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Logo of jnrbmBioMed CentralBiomed Central Web Sitesearchsubmit a manuscriptregisterthis articleJournal of Negative Results in BiomedicineJournal Front Page
J Negat Results Biomed. 2010; 9: 7.
Published online 2010 August 20. doi:  10.1186/1477-5751-9-7
PMCID: PMC2936279

Generation of a panel of antibodies against proteins encoded on human chromosome 21



Down syndrome (DS) is caused by trisomy of all or part of chromosome 21. To further understanding of DS we are working with a mouse model, the Tc1 mouse, which carries most of human chromosome 21 in addition to the normal mouse chromosome complement. This mouse is a model for human DS and recapitulates many of the features of the human syndrome such as specific heart defects, and cerebellar neuronal loss. The Tc1 mouse is mosaic for the human chromosome such that not all cells in the model carry it. Thus to help our investigations we aimed to develop a method to identify cells that carry human chromosome 21 in the Tc1 mouse. To this end, we have generated a panel of antibodies raised against proteins encoded by genes on human chromosome 21 that are known to be expressed in the adult brain of Tc1 mice


We attempted to generate human specific antibodies against proteins encoded by human chromosome 21. We selected proteins that are expressed in the adult brain of Tc1 mice and contain regions of moderate/low homology with the mouse ortholog. We produced antibodies to seven human chromosome 21 encoded proteins. Of these, we successfully generated three antibodies that preferentially recognise human compared with mouse SOD1 and RRP1 proteins on western blots. However, these antibodies did not specifically label cells which carry a freely segregating copy of Hsa21 in the brains of our Tc1 mouse model of DS.


Although we have successfully isolated new antibodies to SOD1 and RRP1 for use on western blots, in our hands these antibodies have not been successfully used for immunohistochemistry studies. These antibodies are freely available to other researchers. Our data high-light the technical difficulty of producing species-specific antibodies for both western blotting and immunohistochemistry.


Down syndrome (DS) is the most common genetic cause of intellectual disability and is also associated with a number of other medical problems including heart defects, early onset Alzheimer's disease and leukaemia [1]. DS is caused by trisomy of human chromosome 21 and is a complex genetic disorder in which the phenotype arises from abnormal dosage of otherwise normal genes.

In order to investigate the relationship between phenotype and causative dosage sensitive genes in DS, we created the Tc1 mouse strain which carries a freely segregating copy of human chromosome 21 (Hsa21) in addition to a full complement of mouse chromosomes [2]. There are deletions in this Hsa21 [2] but at least 83% of the human genes are present in three copies (one human, two endogenous mouse homologs). Therefore, Tc1 mice are trisomic for the majority of genes on Hsa21 and several different investigations have shown they do indeed have phenotypes which are strikingly similar to those found in individuals with DS [2-5].

However, the Tc1 mouse is mosaic for Hsa21, owing to stochastic loss of the human chromosome in cells after fertilisation. Thus the mice have some cells that contain Hsa21 and some that are euploid, which have the normal mouse chromosome complement. The degree of mosaicism differs between tissues and is reported to vary between individual mice; in one survey carried out by genomic quantitative-PCR, on 8 animals, between 7 and 77% of cells in the brain of Tc1 mice carried the Hsa21 (mean 53%) [2]. When chromosome 21 content was assessed directly by fluorescence in situ hybridisation with a human specific probe on metaphase spreads of Tc1 brain cells, between 36 and 94% of the cells carried Hsa21 [2]. Between 2-4% of people with DS also have a mixture of euploid and trisomic cells [6,7]. A low proportion of trisomic cells in these individuals is associated with a reduced severity and incidence of DS associated phenotypes [8]. Additionally, people without DS have also been reported to be mosaic for Hsa21 trisomic cells, in particular individuals with Alzheimer's disease have been reported to have an elevated number of Hsa21 trisomic cells within their brains [9-11]. The phenotypic consequences of these observations have yet to be fully explored.

A study of Hsa21 mosaicism in the Tc1 mouse model may provide insight into these issues. In particular, variability in DS associated phenotypes observed in the Tc1 mouse model may result in part from variation in the number of Hsa21-containing cells in specific tissues and/or cell types. For example, only 73% of Tc1 mice show heart defects at E14.5, whereas the remaining 27% of their genetically identical, Hsa21 positive, littermates do not [2]. This may be due to variable penetrance of the effects of the dosage-sensitive Hsa21 genes, and/or it may be due to mosaicism in the hearts of these animals. In addition, if we could identify Hsa21 positive cells in vivo this may help us investigate the effects of Hsa21 trisomy at the cellular level. Therefore, in an effort to determine which cells in Tc1 mice carry Hsa21 and thus measure levels of mosaicism, we generated antibodies against proteins encoded by Hsa21 that do not cross react with mouse homologues. We focussed our study on proteins expressed in brain as this is our primary organ of interest.

We successfully generated antibodies that preferentially recognised human but not mouse forms of Hsa21-encoded proteins as shown by western blotting. However these antibodies were not compatible with immunohistochemical methods and therefore could not be used to identify individual cells that carry Hsa21. We note that these antibodies are available for other interested laboratories to use.


Choice of candidate proteins

We aimed to generate novel human-specific antibodies raised against proteins encoded on Hsa21 to identify Hsa21 positive cells in our Tc1 mouse model of DS. Our principal goal was to produce a human-specific antibody that did not react with mouse proteins and that was highly expressed in the adult brain as this is our main organ of interest. We used published data and online resources (NCBI- Gene Expression Nervous System Atlas, Affymetrix Symatlas/BioGPS) to identify candidate genes that were reported to be expressed widely in the brain (Table (Table1).1). To avoid generating antibodies against hypothetical proteins we prioritised targets for which there was evidence of a functional protein. Regions of low homology between the human protein and the mouse homologue where then identified by performing Clustal W alignments. In the case of one gene, ADARB1, an exon unique to humans was identified.

Table 1
List of Hsa21 genes present in the Tc1 mouse that are expressed in adult brain.

The secondary structure and accessibility of these low homology regions were modelled using PHD and PROF programmes that were accessed from the Predict Protein website Additionally, the regions were checked against published protein structures to confirm accessibility. The antigenicity of sequences was also estimated using the method of Jameson and Wolf which combines indicators of hydropathy, secondary structure and structural flexibility [12]. Candidate sequences were also checked for consensus sequences for posttranslational modifications including signal sequence cleavage, glycosylation, phosphorylation, and myristoylation using algorithms available from the Predict Protein website [13,14].

Candidate regions that were predicted to be accessible, not post-translationally modified, and exhibited a moderate/high antigenicity index, were checked for similarity with mouse proteins using blastp Those that were highly similar to mouse proteins were discarded as candidates. Ten candidate polypeptide sequences in eight candidate proteins were identified: an RNA editase (ADARB1), a Golgi-resident galactosyltransferase (B3GAL-T5) (two sequences), a potential neurodevelopmental protein (DOPEY2), the Golgi enzyme formimidoyltransferase-cyclodeaminase (FTCD), an RNA processing enzyme (RRP1) (two sequences), superoxide dismutase 1 (SOD1), a cation membrane channel (TRPM2) and a histone deubiquitinase (USP16).

Expression of ADARB1, B3GAL-T5, DOPEY2, FTCD, RRP1, TRPM2 and USP16 was investigated by RT-PCR. Total RNA was isolated from adult Tc1 mouse brain and non-transchromosomic littermate control brain, and subjected to RT-PCR (n = 5). Significant expression of FTCD could not be detected in human or Tc1 brain (Figure (Figure1D).1D). Therefore the two identified FTCD polypeptide sequences were discarded as potential candidates against which to raise an antibody. The expression of the other genes of interest was confirmed in the Tc1 brain (Figure (Figure1).1). Elevated expression of SOD1 in the Tc1 brain had been previously demonstrated by western blot [2].

Figure 1
Expression of candidate Hsa21 genes in the Tc1 adult brain. To determine if the candidate genes were expressed, RT-PCR was undertaken using primers against (B) USP16 (129 base pair product), (C) B3GAL-T5 (138 base pair product), (D) DOPEY2 (192 base pair ...

Production, conjugation of the selected peptides to Keyhole limpet haemocyanin (KHL) and injection of the KHL-peptides into New Zealand Rabbits was undertaken (21st Century Biochemicals). In the case of B3GAL-T5 and RRP1 a mixture of two peptides were injected into each rabbit (Table (Table2).2). Sera isolated from the rabbits after the fifth, sixth and seventh KHL-peptide boost was affinity purified against the peptide. Sera from the rabbits challenged with B3GAL-T5 and RRP1 peptides were affinity purified against both peptides separately.

Table 2
List of Hsa21 Genes and peptides used to immunise rabbits.

Antibodies that recognise a Tc1 Hsa21 specific protein


One of the anti-RRP1 antibodies (9644-B), which was purified against peptide B, recognised a 50 kDa band on western blots of Tc1 total brain proteins; consistent with the predicted molecular weight of RRP1 (Figure (Figure2A).2A). A similar band was not observed in non-transchromosomic control mice, indicating that this antibody may specifically react with human RRP1. RRP1 peptide sequence B is unique to the human protein and is not found in mouse RRP1. In addition to the Tc1 specific band a number of weaker additional bands were observed in samples of Tc1 and non-Tc1 total brain proteins. These are likely to represent non-specific interaction of the polyclonal antibody with other brain proteins. Despite the relative specificity of the 9644-B antibody on western blot, a similar pattern and intensity of staining was observed on Tc1 and non-transchromosomic control mouse whole brain sections; intracellular staining was observed through-out the brain in both Tc1 and control non-transchromosomic mice (Figure (Figure3A3A and and3B).3B). Therefore, although 9644-B may be a suitable antibody for western blot studies of RRP1, it cannot be used to identify Hsa21 positive cells in the brains of Tc1 mice.

Figure 2
Western blot of total brain proteins probed with affinity purified rabbit polyclonal antibodies. Total brain proteins from Tc1 adult mice (Tc1+), non-transchromosomic littermate control mice (C), transgenic mice that express wild type human SOD1 (Tg(SOD1)2Gur), ...
Figure 3
Affinity purified anti-RRP1 and SOD1 antibodies do not specifically label cells in the Tc1 mouse model. A similar pattern and intensity of staining is observed in adult Tc1 (A, C, E) and non-transchromosomic littermate control (B, D, F) cortical brain ...

Affinity purified antibody raised against RRP1 peptide B purified from the second rabbit (9643-B) did not recognise a Tc1 specific band (Figure (Figure2B).2B). A 50 kDa protein was weakly detected using this antibody in samples of Tc1 and control mouse brain; however, peptide B does not share any homology with mouse RRP1 therefore the 50 kDa band detected after probing with this antibody is highly unlikely to be RRP1.

An antibody affinity purified against RRP1 peptide A (9644-A) did recognise a band consistent with the molecular weight of RRP1 in samples of both Tc1 and control brain (Figure (Figure2C).2C). Five of the nineteen amino acids of peptide A are homologous with the mouse RRP1 protein sequence including a sequence (K*PA) with high predicted antigenicity. Therefore the antibody purified against peptide A may recognise both mouse and human RRP1 and therefore is not useful to identify Hsa21 positive cells in the Tc1 model. An antibody affinity purified against peptide A from the other rabbit (9643-B) did not consistently recognise a band corresponding to the molecular weight of RRP1 (Figure (Figure2D).2D). This suggests that RRP1 peptide A is not a reliable antigen for the production of rabbit polyclonal antibodies.

Antibodies that did not recognise a Tc1 unique product


Immunisation with a single SOD1 peptide generated anti-SOD1 antibodies (9638 and 9637) that recognised a Tc1 specific band on western blots of total brain protein (Figure (Figure2E2E and and2F).2F). The size of the bands recognised is consistent with the known molecular weight of the SOD1 monomer (16 kDa). These antibodies also detected a band of a comparable molecular weight in samples of total brain proteins isolated from transgenic mice that over-express wild-type or mutant (SOD1G93A) human SOD1 and in samples of recombinant human SOD1 (wild-type or SOD1G93A) (gift of Ruth Chia) (Figure (Figure2E2E and and2F).2F). The 16 kDa band was not observed in samples of brain from non-transchromosomic control mice. However, after long exposures a weak band that was smaller than the predominant 16 kDa band was detected by both 9637 and 9638 in Tc1 and control mouse brain samples. This smaller band may be mouse SOD1; thus antibody 9637 and 9638 may weakly cross-react with mouse SOD1. Moreover, these antibodies generated an intracellular staining pattern of similar intensity on Tc1 and non-transchromosomic control mice brain sections, which were either paraffin-embedded or cryopreserved (Figure 3C-F, data not shown). The antibody does not recognise cells specifically in the Tc1 brain and therefore cannot be used to identify these Hsa21 positive cells in our mouse model for future studies. This result may occur because the polyclonal antibodies generated recognise non-SOD1 proteins and weakly cross-react with mouse SOD1 in both Tc1 and control brain, or that the antibodies generated only recognise denatured human SOD1. We have previously tested whether a number of commercially available anti-SOD1 antibodies specifically label cells in Tc1 brain sections and found that these antibodies were not specific (data not shown).


An affinity purified antibody (9528) that reacted weakly with a band consistent with the known molecular weight of the protein, 80 kDa, was isolated from one rabbit injected with the ADARB1 peptide (Figure (Figure2G).2G). However, this band was observed in samples of total brain proteins from both Tc1 and non-transchromosomic control mice. As ADARB1 peptide sequence used to challenge the rabbits was unique to human ADARB1 and not found in mouse, the protein recognised by this antibody is unlikely to be ADARB1. No signal consistent with the molecular weight of ADARB1 was observed when western blots of total brain proteins were probed with affinity purified antibody generated from the second rabbit (9529), which was challenged with ADARB1 peptide (data not shown).


Affinity purified antibodies raised against B3GAL-T5 peptides were used to probe western blots of total brain proteins from Tc1 and control mice and recombinant glutathione-S-transferase (GST) tagged human B3GAL-T5 (amino acids 29-128, Abnova). Recombinant human B3GAL-T5 was detected using both antibodies (Figure (Figure2H2H and and2I).2I). A predominant band of 64 kDa and weaker bands of around 50 kDa were detected in western blots of Tc1 and control samples probed with antibodies affinity purified against peptide A (9598-A) (Figure (Figure2H).2H). A predominant band of 50 kDa and weaker bands of 64, 36 and approximately 28 kDa were detected in western blots of samples of total brain proteins from Tc1 and control mice that were probed with antibodies affinity purified against peptide B (9598-B) (Figure (Figure2I).2I). The molecular weight of human B3GAL-T5 is 36 kDa. However, B3GAL-T5 contains three N-glycosylation sequences (amino acids 130, 174 and 231) that may be occupied in vivo. Indeed in COS-7 cells a variety of B3GAL-T5 glycoforms of between 37-50 kDa are detected by western blot [15]. To investigate if the protein bands detected in samples of Tc1 and control brain are glycosylated forms of B3GAL-T5 samples of Tc1 and control brain proteins were treated with PNGase F, an enzyme that cleaves protein-attached N-linked glycans, before western blotting. De-glycosylation of endogenous proteins was confirmed by checking that the glycoprotein PrP exhibited the expected size shift after PNGase F treatment (data not shown). Enrichment of a 36 kDa protein was observed in Tc1 and control brain samples after treatment PNGase F on western blots probed with the antibody affinity purified against peptide A (9598-A), consistent with this antibody recognising endogenous B3GAL-T5 (Figure (Figure2H).2H). No enrichment in a 36 kDa band was observed in the brain samples treated with PNGase F that were probed with the antibody affinity purified against peptide B (9598-B) (Figure (Figure2I).2I). This result suggests that the 50 kDa protein recognised by antibody 9598-B is not a glycosylated form of B3GAL-T5.


Affinity purified rabbit polyclonal antibodies raised against DOPEY2 and TRPM2 and USP16 peptides did not react with a band of the predicted molecular weight, in western blots of Tc1 and non-transchromosomic control total brain proteins (data not shown). In addition the pattern and intensity of staining observed in Tc1 and non-transchromosomic control paraffin-embedded or cryopreserved brain sections was similar, indicating that that these antibodies do not recognise a Hsa21 specific product (data not shown).


In order to specifically detect cells carrying Hsa21 in our Tc1 mice, we carried out extensive literature searches of both commercial and basic research resources and were unable to find suitable antibodies that could be used on fixed tissues and primary cell cultures. Many antibodies to Hsa21 derived proteins exist, but none that we could find specifically recognised Hsa21 positive cells in Tc1 mouse brain sections and not control non-transchromosomic mouse sections. Therefore we attempted to generate Hsa21 antibodies that we could use to identify Hsa21 carrying cells in our model.

From bioinformatics analysis, we identified eight genes which were present in the Tc1 mouse and which might make suitable candidates for further analysis. One of these, FTCD, was not expressed in brain and so we generated eighteen different antibodies raised against amino-acid sequences identified from the remaining seven genes, selecting only sequences which were divergent between mouse and human, and likely to be moderately/highly antigenic.

We generated a panel of antibodies, of which one antibody (9644-B) raised against RRP1 appeared to be human specific on western blots, although proved unsuitable for immunohistochemistry and two new antibodies raised against SOD1 (9638 and 9637) that appear to preferentially recognise human SOD1 on western blots, but do not recognise Hsa21 positive cells in Tc1 brains by immunohistochemistry.


Having surveyed 295 genes on Hsa21 we are left with three antibodies that we can use for western blot analysis that will preferentially bind to human protein, and none that will work by immunohistochemistry. This illustrates the difficulty of making antibodies that only recognise a specific human protein but not its mouse homologue, even with extensive knowledge of the genes available, their likely antigenicity and the degree of conservation between mouse and human. We will now go on to other methods for detecting Hsa21 in tissue sections and cultured cells, and we note that the antibodies we have generated are available to interested laboratories.


Animal Welfare

Mice were housed in controlled conditions in accordance with guidance issued by the Medical Research Council in Responsibility in the Use of Animals for Medical Research (1993) and all experiments were carried out under License from the UK Home Office.

DNA extraction and Genotyping

DNA was extracted from tail tip (approximately 3mm) from all samples analysed. Tail tip is lysed overnight using Proteinase K digestion in nuclei lysis buffer (Promega), plus 0.12 M EDTA at 55°C. Proteins are precipitated from the resultant lysate by addition of protein precipitation solution (Promega), DNA is then precipitated with isopropanol and resuspended in DNase free water. Tc1 mice were genotyped using PCR (Tc1 specific primers f: 5'-GGTTTGAGGGAACACAAAGCTTAACTCCCA-3' r: 5'-ACAGAGCTACAGCCTCTGACACTATGAACT-3', control primers f: 5'-TTACGTCCATCGTGGACAGCAT-3' r: 5'-TGGGCTGGGTGTTAGTCTTAT-3'). Tc1 mice were taken from a colony maintained by mating Tc1 females to F1(129S8 × C57BL/6) males. Both SOD1 transgenics were taken from colonies maintained by crossing male transgenics to female C57BL6/J (Jackson Laboratories, Bar Harbour). SOD1 transgenic mice (Tg(SOD1)2Gur, Jackson and Tg(SOD1*G93A)1Gur; Jackson Laboratories, Bar Harbour) were genotyped by PCR (SOD1 specific primers f: 5'-CATCAGCCC TAATCCATCTGA-3' r: 5'-CGCGACTAACAATCAAAGTGA-3', control primers f: 5'-CTAGGCCACAGAATTGAAAGATCT-3' r: 5'-GTAGGTGGAAATTCTAGCATCATC-3').

RNA extraction and RT-PCR

RNA was extracted from whole brains from 6-10 week old Tc1 and age and sex matched non-transchromosomic controls. Total RNA was extracted using TRIzol reagent (Invitrogen), precipitated as per manufactures instructions and resuspended in DNase-free water. Amounts of RNA were equalised and cDNA was generated using a standard reverse-transcription protocol using random primers (Promega), Superscript II (Invitrogen), First Strand Buffer (Invitrogen) and dNTPs (Promega). PCR using primers which amplify a PCR product from both mouse Dyrk1A and human DYKR1A (f: 5'-GGAGAGACTTCAGCATGCAAAC-3' r: 5'-GCTGGGTCACGGAAGGTTTG-3') or mouse DYRK1A (f: 5'-CAAGAAAACAGCTGATGAAGG-3' r: 5'-AGCCCCTTGTCTCATCGC-3') were used to check cDNA. PCR using primers designed to raised a product against human but not mouse FTCD (f: 5'-GAATGCGTCCCCAACTTTTCG-3' r: 5'-GTCGATAAGTCGGGAAGCTAC-3'), USP16 (f: 5'-AAGCCTTCAGTTTGGCTG-3' r: 5'-GTCCAAACTAAGAACCAGAC-3'), DOPEY2 (f: 5'-ACCTGAGGTACTCCTTGTTG-3' r: 5'-CCAGGAGAGGAAATAACCCG-3'), TRPM2 (f: 5'-GTTCGTGGATTCCTGAAAAC-3' r: 5'-TCCAAGTGCTGCTCATGC-3' and f: 5'-TGGCCGTCAGCGTCCACTTC-3' r: 5'-TAGTGAGCCCCGAACTCAGC-3'), B3GAL-T5 (f: 5'-CACTGTGGCTTTAGCTTTCAAAC-3' r: 5'-GGATTTAGACTGTACATGC-3'), ADARB1 (f: 5'-TTTAGGCTGAAGGAGAATGTC-3' r: 5'-CCTCTTGCTTTACGATTTGGG-3' and f: 5'-GTCTCGCTCTTACACCCAG-3' r: 5'-CCTCTTGCTTTACGATTTGGG-3') and RRP1 (f: 5'-TCCCTGAAGATGAGATCCCAG-3' r: 5'-TACACCCCTCCTCCTGCTC-3') were used to check the expression of these genes from Hsa21.

Western blotting

Whole brain from Tc1, Tg(SOD1)2Gur, Tg(SOD1*G93A)1Gur and aged and sex matched control non-transgenic mice was homogenized in 9 volumes of RIPA Buffer (150 mM sodium chloride, 50 mM Tris, 1% NP-40, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulfate) or phosphate buffered saline plus complete protease inhibitors (PBS) (Roche Applied Science) by mechanical disruption using a dounce homogenizer. Total protein content was determined using the DC protein Assay (Biorad). Samples that were homogenized in PBS were treated with PNGase F (15 U/μg protein) (New England Biolabs) for 3 hours shaking at 37°C to cleave N-linked glycans. The resultant total brain protein and recombinant protein samples were denatured in SDS denaturing buffer (Invitrogen) and β-mercaptoethanol for 10 minutes at 100°C, prior to separation by SDS-PAGE gel electrophoresis using precast 16% or 4-20% Tris-glycine gels (Invitrogen). Proteins were transferred to PVDF membrane prior to blocking in 5% milk PBS for 1 hour before incubating over-night with primary antibody at 4°C. Membranes were then incubated with an anti-rabbit secondary antibody (Sigma-Aldrich) conjugated to alkaline phosphatase prior to development with CDP-Star (Roche Applied Sciences) and exposure to X-ray film. See-Blue plus 2 (Invitrogen) was used as a molecular weight marker.


Whole Tc1 and non-transchromosomic control mouse brain was fixed by immersion in 10% buffered formal saline (Pioneer Research Chemicals). Following further washing for 24 hr in 10% buffered formal saline, tissue samples were processed and embedded in paraffin wax. Sections were cut at a thickness of 4 μm. Alternatively brains were protected in Tissue-Tek (Siemens Healthcare Diagnostics) and frozen by immersion in isopentane chilled with liquid nitrogen. Frozen sections were cut at a thickness of 10 μm on a cryostat and air dried prior to staining. Paraffin-embedded sections were pretreated by protease digestion. Staining with the rabbit polyclonal antibodies was undertaken using a Ventana automated immunohistochemical staining machine (Ventana Medical Systems, Tuscon, AZ, USA) as described previously [16]. A biotinylated-anti-rabbit IgG secondary antibody (iView SA-HRP, Ventana Medical Systems) was used before development with 3'3 diaminobenzidine tetrachloride as the chromogen (iView DAB, Ventana Medical Systems). Haematoxylin was used as the counter-stain.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

FW carried out the bioinformatic searches, immunohistochemistry and some RT-PCRs and western blots, analysed the data and assisted in drafting the manuscript. OS carried out the some RT-PCRs and western blots and assisted in drafting the manuscript. JL and SB assisted with IHC data collection and analysis. EF and VT conceived the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript


We thank Ray Young for help with preparation of the figures and Ruth Chia for recombinant SOD1 proteins. VLJT is funded by the UK Medical Research Council, the AnEUploidy grant from Framework Programme 6 from the European Union Commission, the Leukaemia Research Fund and the Wellcome Trust; FKW, OS and EMCF are funded by the UK Medical Research Council, the Wellcome Trust, the AnEUploidy grant from Framework Programme 6 from the European Union Commission and the Fidelity Foundation. These funding bodies had no role in the design of this study or the decision to publish these data.


  • Wiseman FK, Alford KA, Tybulewicz VL, Fisher EM. Down syndrome--recent progress and future prospects. Hum Mol Genet. 2009;18:R75–R83. doi: 10.1093/hmg/ddp010. [PMC free article] [PubMed] [Cross Ref]
  • O'Doherty A, Ruf S, Mulligan C, Hildreth V, Errington ML, Cooke S, Sesay A, Modino S, Vanes L, Hernandez D. et al. An aneuploid mouse strain carrying human chromosome 21 with down syndrome phenotypes. Science. 2005;309:2033–2037. doi: 10.1126/science.1114535. [PMC free article] [PubMed] [Cross Ref]
  • Galante M, Jani H, Vanes L, Daniel H, Fisher EM, Tybulewicz VL, Bliss TV, Morice E. Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome. Hum Mol Genet. 2009;18:1449–1463. doi: 10.1093/hmg/ddp055. [PMC free article] [PubMed] [Cross Ref]
  • Morice E, Andreae LC, Cooke SF, Vanes L, Fisher EM, Tybulewicz VL, Bliss TV. Preservation of long-term memory and synaptic plasticity despite short-term impairments in the Tc1 mouse model of Down syndrome. Learn Mem. 2008;15:492–500. doi: 10.1101/lm.969608. [PubMed] [Cross Ref]
  • Reynolds LE, Watson AR, Baker M, Jones TA, D'Amico G, Robinson SD, Joffre C, Garrido-Urbani S, Rodriguez-Manzaneque JC, Martino-Echarri E. et al. Tumour angiogenesis is reduced in the Tc1 mouse model of Down's syndrome. Nature. 2010;465:813–817. doi: 10.1038/nature09106. [PubMed] [Cross Ref]
  • Stoll C, Alembik Y, Dott B, Roth MP. Study of Down syndrome in 238,942 consecutive births. Ann Genet. 1998;41:44–51. [PubMed]
  • Devlin L, Morrison PJ. Mosaic Down's syndrome prevalence in a complete population study. Arch Dis Child. 2004;89:1177–1178. doi: 10.1136/adc.2003.031765. [PMC free article] [PubMed] [Cross Ref]
  • Papavassiliou P, York TP, Gursoy N, Hill G, Nicely LV, Sundaram U, McClain A, Aggen SH, Eaves L, Riley B. et al. The phenotype of persons having mosaicism for trisomy 21/Down syndrome reflects the percentage of trisomic cells present in different tissues. Am J Med Genet A. 2009;149A:573–583. doi: 10.1002/ajmg.a.32729. [PubMed] [Cross Ref]
  • Kingsbury MA, Friedman B, McConnell MJ, Rehen SK, Yang AH, Kaushal D, Chun J. Aneuploid neurons are functionally active and integrated into brain circuitry. Proc Natl Acad Sci USA. 2005;102:6143–6147. doi: 10.1073/pnas.0408171102. [PubMed] [Cross Ref]
  • Rehen SK, Yung YC, McCreight MP, Kaushal D, Yang AH, Almeida BS, Kingsbury MA, Cabral KM, McConnell MJ, Anliker B. et al. Constitutional aneuploidy in the normal human brain. J Neurosci. 2005;25:2176–2180. doi: 10.1523/JNEUROSCI.4560-04.2005. [PubMed] [Cross Ref]
  • Kingsbury MA, Yung YC, Peterson SE, Westra JW, Chun J. Aneuploidy in the normal and diseased brain. Cell Mol Life Sci. 2006;63:2626–2641. doi: 10.1007/s00018-006-6169-5. [PubMed] [Cross Ref]
  • Jameson BA, Wolf H. The antigenic index: a novel algorithm for predicting antigenic determinants. Comput Appl Biosci. 1988;4:181–186. [PubMed]
  • Claros MG, Vincens P. Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur J Biochem. 1996;241:779–786. doi: 10.1111/j.1432-1033.1996.00779.x. [PubMed] [Cross Ref]
  • Emanuelsson O, Brunak S, von Heijne G, Nielsen H. Locating proteins in the cell using TargetP, SignalP and related tools. Nat Protoc. 2007;2:953–971. doi: 10.1038/nprot.2007.131. [PubMed] [Cross Ref]
  • Seko A, Kataoka F, Aoki D, Sakamoto M, Nakamura T, Hatae M, Yonezawa S, Yamashita K. Beta1,3-galactosyltransferases-4/5 are novel tumor markers for gynecological cancers. Tumour Biol. 2009;30:43–50. doi: 10.1159/000203129. [PubMed] [Cross Ref]
  • Wadsworth JD, Powell C, Beck JA, Joiner S, Linehan JM, Brandner S, Mead S, Collinge J. Molecular diagnosis of human prion disease. Methods Mol Biol. 2008;459:197–227. full_text. [PubMed]
  • Otterson GA, Flynn GC, Kratzke RA, Coxon A, Johnston PG, Kaye FJ. Stch encodes the 'ATPase core' of a microsomal stress 70 protein. EMBO J. 1994;13:1216–1225. [PubMed]
  • Sultan M, Piccini I, Balzereit D, Herwig R, Saran NG, Lehrach H, Reeves RH, Yaspo ML. Gene expression variation in Down's syndrome mice allows prioritization of candidate genes. Genome Biol. 2007;8:R91. doi: 10.1186/gb-2007-8-5-r91. [PMC free article] [PubMed] [Cross Ref]
  • Valero R, Marfany G, Gonzalez-Angulo O, Gonzalez-Gonzalez G, Puelles L, Gonzalez-Duarte R. USP25, a novel gene encoding a deubiquitinating enzyme, is located in the gene-poor region 21q11.2. Genomics. 1999;62:395–405. doi: 10.1006/geno.1999.6025. [PubMed] [Cross Ref]
  • Valero R, Bayes M, Francisca Sanchez-Font M, Gonzalez-Angulo O, Gonzalez-Duarte R, Marfany G. Characterization of alternatively spliced products and tissue-specific isoforms of USP28 and USP25. Genome Biol. 2001;2:RESEARCH0043. doi: 10.1186/gb-2001-2-10-research0043. [PMC free article] [PubMed] [Cross Ref]
  • Lockstone HE, Harris LW, Swatton JE, Wayland MT, Holland AJ, Bahn S. Gene expression profiling in the adult Down syndrome brain. Genomics. 2007;90:647–660. doi: 10.1016/j.ygeno.2007.08.005. [PubMed] [Cross Ref]
  • Palmeri D, van Zante A, Huang CC, Hemmerich S, Rosen SD. Vascular endothelial junction-associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular boundaries of endothelial cells. J Biol Chem. 2000;275:19139–19145. doi: 10.1074/jbc.M003189200. [PubMed] [Cross Ref]
  • Aurrand-Lions M, Johnson-Leger C, Wong C, Du PL, Imhof BA. Heterogeneity of endothelial junctions is reflected by differential expression and specific subcellular localization of the three JAM family members. Blood. 2001;98:3699–3707. doi: 10.1182/blood.V98.13.3699. [PubMed] [Cross Ref]
  • McCulloch DR, Le Goff C, Bhatt S, Dixon LJ, Sandy JD, Apte SS. Adamts5, the gene encoding a proteoglycan-degrading metalloprotease, is expressed by specific cell lineages during mouse embryonic development and in adult tissues. Gene Expr Patterns. 2009;9:314–323. doi: 10.1016/j.gep.2009.02.006. [PMC free article] [PubMed] [Cross Ref]
  • Gunther W, Skaftnesmo KO, Arnold H, Bjerkvig R, Terzis AJ. Distribution patterns of the anti-angiogenic protein ADAMTS-1 during rat development. Acta Histochem. 2005;107:121–131. doi: 10.1016/j.acthis.2004.07.009. [PubMed] [Cross Ref]
  • Kubota H, Hynes G, Willison K. The eighth Cct gene, Cctq, encoding the theta subunit of the cytosolic chaperonin containing TCP-1. Gene. 1995;154:231–236. doi: 10.1016/0378-1119(94)00880-2. [PubMed] [Cross Ref]
  • Kubota H, Yokota S, Yanagi H, Yura T. Structures and co-regulated expression of the genes encoding mouse cytosolic chaperonin CCT subunits. Eur J Biochem. 1999;262:492–500. doi: 10.1046/j.1432-1327.1999.00405.x. [PubMed] [Cross Ref]
  • Sakoda E, Igarashi K, Sun J, Kurisu K, Tashiro S. Regulation of heme oxygenase-1 by transcription factor Bach1 in the mouse brain. Neurosci Lett. 2008;440:160–165. doi: 10.1016/j.neulet.2008.04.082. [PubMed] [Cross Ref]
  • Choi KH, Zepp ME, Higgs BW, Weickert CS, Webster MJ. Expression profiles of schizophrenia susceptibility genes during human prefrontal cortical development. J Psychiatry Neurosci. 2009;34:450–458. [PMC free article] [PubMed]
  • Mozhui K, Karlsson RM, Kash TL, Ihne J, Norcross M, Patel S, Farrell MR, Hill EE, Graybeal C, Martin KP. et al. Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability. J Neurosci. 2010;30:5357–5367. doi: 10.1523/JNEUROSCI.5017-09.2010. [PMC free article] [PubMed] [Cross Ref]
  • Gulesserian T, Seidl R, Hardmeier R, Cairns N, Lubec G. Superoxide dismutase SOD1, encoded on chromosome 21, but not SOD2 is overexpressed in brains of patients with Down syndrome. J Investig Med. 2001;49:41–46. doi: 10.2310/6650.2001.34089. [PubMed] [Cross Ref]
  • de Haan JB, Newman JD, Kola I. Cu/Zn superoxide dismutase mRNA and enzyme activity, and susceptibility to lipid peroxidation, increases with aging in murine brains. Brain Res Mol Brain Res. 1992;13:179–187. doi: 10.1016/0169-328X(92)90025-7. [PubMed] [Cross Ref]
  • Shin JH, Krapfenbauer K, Lubec G. Mass-spectrometrical analysis of proteins encoded on chromosome 21 in human fetal brain. Amino Acids. 2006;31:435–447. doi: 10.1007/s00726-005-0257-y. [PubMed] [Cross Ref]
  • Tobin JE, Cui J, Wilk JB, Latourelle JC, Laramie JM, McKee AC, Guttman M, Karamohamed S, DeStefano AL, Myers RH. Sepiapterin reductase expression is increased in Parkinson's disease brain tissue. Brain Res. 2007;1139:42–47. doi: 10.1016/j.brainres.2007.01.001. [PMC free article] [PubMed] [Cross Ref]
  • Rachidi M, Lopes C, Delezoide AL, Delabar JM. C21orf5, a human candidate gene for brain abnormalities and mental retardation in Down syndrome. Cytogenet Genome Res. 2006;112:16–22. doi: 10.1159/000087509. [PubMed] [Cross Ref]
  • Rachidi M, Lopes C, Costantine M, Delabar JM. C21orf5, a new member of Dopey family involved in morphogenesis, could participate in neurological alterations and mental retardation in Down syndrome. DNA Res. 2005;12:203–210. doi: 10.1093/dnares/dsi004. [PubMed] [Cross Ref]
  • Rachidi M, Delezoide AL, Delabar JM, Lopes C. A quantitative assessment of gene expression (QAGE) reveals differential overexpression of DOPEY2, a candidate gene for mental retardation, in Down syndrome brain regions. Int J Dev Neurosci. 2009;27:393–398. doi: 10.1016/j.ijdevneu.2009.02.001. [PubMed] [Cross Ref]
  • Lopes C, Chettouh Z, Delabar JM, Rachidi M. The differentially expressed C21orf5 gene in the medial temporal-lobe system could play a role in mental retardation in Down syndrome and transgenic mice. Biochem Biophys Res Commun. 2003;305:915–924. doi: 10.1016/S0006-291X(03)00867-2. [PubMed] [Cross Ref]
  • Metz RP, Kwak HI, Gustafson T, Laffin B, Porter WW. Differential transcriptional regulation by mouse single-minded 2s. J Biol Chem. 2006;281:10839–10848. doi: 10.1074/jbc.M508858200. [PubMed] [Cross Ref]
  • Ema M, Ikegami S, Hosoya T, Mimura J, Ohtani H, Nakao K, Inokuchi K, Katsuki M, Fujii-Kuriyama Y. Mild impairment of learning and memory in mice overexpressing the mSim2 gene located on chromosome 16: an animal model of Down's syndrome. Hum Mol Genet. 1999;8:1409–1415. doi: 10.1093/hmg/8.8.1409. [PubMed] [Cross Ref]
  • Fan CM, Kuwana E, Bulfone A, Fletcher CF, Copeland NG, Jenkins NA, Crews S, Martinez S, Puelles L, Rubenstein JL. et al. Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of Down syndrome. Mol Cell Neurosci. 1996;7:1–16. doi: 10.1006/mcne.1996.0001. [PubMed] [Cross Ref]
  • Nakamura A, Hattori M, Sakaki Y. Isolation of a novel human gene from the Down syndrome critical region of chromosome 21q22.2. J Biochem. 1997;122:872–877. [PubMed]
  • Ferrer I, Barrachina M, Puig B, Martinez dL, Marti E, Avila J, Dierssen M. Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis. 2005;20:392–400. doi: 10.1016/j.nbd.2005.03.020. [PubMed] [Cross Ref]
  • Marti E, Altafaj X, Dierssen M, de la LS, Fotaki V, Alvarez M, Perez-Riba M, Ferrer I, Estivill X. Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous system. Brain Res. 2003;964:250–263. doi: 10.1016/S0006-8993(02)04069-6. [PubMed] [Cross Ref]
  • Wegiel J, Kuchna I, Nowicki K, Frackowiak J, Dowjat K, Silverman WP, Reisberg B, Deleon M, Wisniewski T, Adayev T. et al. Cell type- and brain structure-specific patterns of distribution of minibrain kinase in human brain. Brain Res. 2004;1010:69–80. doi: 10.1016/j.brainres.2004.03.008. [PubMed] [Cross Ref]
  • Harashima C, Jacobowitz DM, Witta J, Borke RC, Best TK, Siarey RJ, Galdzicki Z. Abnormal expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in hippocampus, frontal cortex, and substantia nigra of Ts65Dn mouse: a model of Down syndrome. J Comp Neurol. 2006;494:815–833. doi: 10.1002/cne.20844. [PMC free article] [PubMed] [Cross Ref]
  • Schein JC, Hunter DD, Roffler-Tarlov S. Girk2 expression in the ventral midbrain, cerebellum, and olfactory bulb and its relationship to the murine mutation weaver. Dev Biol. 1998;204:432–450. doi: 10.1006/dbio.1998.9076. [PubMed] [Cross Ref]
  • Wei J, Hodes ME, Piva R, Feng Y, Wang Y, Ghetti B, Dlouhy SR. Characterization of murine Girk2 transcript isoforms: structure and differential expression. Genomics. 1998;51:379–390. doi: 10.1006/geno.1998.5369. [PubMed] [Cross Ref]
  • Greber-Platzer S, Schatzmann-Turhani D, Cairns N, Balcz B, Lubec G. Expression of the transcription factor ETS2 in brain of patients with Down syndrome--evidence against the overexpression-gene dosage hypothesis. J Neural Transm Suppl. 1999;57:269–281. [PubMed]
  • Vidal-Taboada JM, Lu A, Pique M, Pons G, Gil J, Oliva R. Down syndrome critical region gene 2: expression during mouse development and in human cell lines indicates a function related to cell proliferation. Biochem Biophys Res Commun. 2000;272:156–163. doi: 10.1006/bbrc.2000.2726. [PubMed] [Cross Ref]
  • Dunn CA, Medstrand P, Mager DL. An endogenous retroviral long terminal repeat is the dominant promoter for human beta1,3-galactosyltransferase 5 in the colon. Proc Natl Acad Sci USA. 2003;100:12841–12846. doi: 10.1073/pnas.2134464100. [PubMed] [Cross Ref]
  • Ziai MR, Sangameswaran L, Hempstead JL, Danho W, Morgan JI. An immunochemical analysis of the distribution of a brain-specific polypeptide, PEP-19. J Neurochem. 1988;51:1771–1776. doi: 10.1111/j.1471-4159.1988.tb01158.x. [PubMed] [Cross Ref]
  • Ziai R, Pan YC, Hulmes JD, Sangameswaran L, Morgan JI. Isolation, sequence, and developmental profile of a brain-specific polypeptide, PEP-19. Proc Natl Acad Sci USA. 1986;83:8420–8423. doi: 10.1073/pnas.83.21.8420. [PubMed] [Cross Ref]
  • Utal AK, Stopka AL, Roy M, Coleman PD. PEP-19 immunohistochemistry defines the basal ganglia and associated structures in the adult human brain, and is dramatically reduced in Huntington's disease. Neuroscience. 1998;86:1055–1063. doi: 10.1016/S0306-4522(98)00130-4. [PubMed] [Cross Ref]
  • Saito Y, Oka A, Mizuguchi M, Motonaga K, Mori Y, Becker LE, Arima K, Miyauchi J, Takashima S. The developmental and aging changes of Down's syndrome cell adhesion molecule expression in normal and Down's syndrome brains. Acta Neuropathol. 2000;100:654–664. doi: 10.1007/s004010000230. [PubMed] [Cross Ref]
  • Barlow GM, Chen XN, Shi ZY, Lyons GE, Kurnit DM, Celle L, Spinner NB, Zackai E, Pettenati MJ, Van Riper AJ. et al. Down syndrome congenital heart disease: a narrowed region and a candidate gene. Genet Med. 2001;3:91–101. doi: 10.1097/00125817-200103000-00002. [PubMed] [Cross Ref]
  • Bennett BD, Babu-Khan S, Loeloff R, Louis JC, Curran E, Citron M, Vassar R. Expression analysis of BACE2 in brain and peripheral tissues. J Biol Chem. 2000;275:20647–20651. doi: 10.1074/jbc.M002688200. [PubMed] [Cross Ref]
  • Hussain I, Powell DJ, Howlett DR, Chapman GA, Gilmour L, Murdock PR, Tew DG, Meek TD, Chapman C, Schneider K. et al. ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site. Mol Cell Neurosci. 2000;16:609–619. doi: 10.1006/mcne.2000.0884. [PubMed] [Cross Ref]
  • Barbiero L, Benussi L, Ghidoni R, Alberici A, Russo C, Schettini G, Pagano SF, Parati EA, Mazzoli F, Nicosia F. et al. BACE-2 is overexpressed in Down's syndrome. Exp Neurol. 2003;182:335–345. doi: 10.1016/S0014-4886(03)00049-9. [PubMed] [Cross Ref]
  • Motonaga K, Itoh M, Becker LE, Goto Y, Takashima S. Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in brains of patients with Down syndrome. Neurosci Lett. 2002;326:64–66. doi: 10.1016/S0304-3940(02)00287-2. [PubMed] [Cross Ref]
  • Di Schiavi E, Riano E, Heye B, Bazzicalupo P, Rugarli EI. UMODL1/Olfactorin is an extracellular membrane-bound molecule with a restricted spatial expression in olfactory and vomeronasal neurons. Eur J Neurosci. 2005;21:3291–3300. doi: 10.1111/j.1460-9568.2005.04164.x. [PubMed] [Cross Ref]
  • Tachikawa M, Watanabe M, Hori S, Fukaya M, Ohtsuki S, Asashima T, Terasaki T. Distinct spatio-temporal expression of ABCA and ABCG transporters in the developing and adult mouse brain. J Neurochem. 2005;95:294–304. doi: 10.1111/j.1471-4159.2005.03369.x. [PubMed] [Cross Ref]
  • Tarr PT, Edwards PA. ABCG1 and ABCG4 are coexpressed in neurons and astrocytes of the CNS and regulate cholesterol homeostasis through SREBP-2. J Lipid Res. 2008;49:169–182. doi: 10.1194/jlr.M700364-JLR200. [PubMed] [Cross Ref]
  • Michaud J, Kudoh J, Berry A, Bonne-Tamir B, Lalioti MD, Rossier C, Shibuya K, Kawasaki K, Asakawa S, Minoshima S. et al. Isolation and characterization of a human chromosome 21q22.3 gene (WDR4) and its mouse homologue that code for a WD-repeat protein. Genomics. 2000;68:71–79. doi: 10.1006/geno.2000.6258. [PubMed] [Cross Ref]
  • Chen H, Rossier C, Nakamura Y, Lynn A, Chakravarti A, Antonarakis SE. Cloning of a novel homeobox-containing gene, PKNOX1, and mapping to human chromosome 21q22.3. Genomics. 1997;41:193–200. doi: 10.1006/geno.1997.4632. [PubMed] [Cross Ref]
  • Ferretti E, Schulz H, Talarico D, Blasi F, Berthelsen J. The PBX-regulating protein PREP1 is present in different PBX-complexed forms in mouse. Mech Dev. 1999;83:53–64. doi: 10.1016/S0925-4773(99)00031-3. [PubMed] [Cross Ref]
  • Enokido Y, Suzuki E, Iwasawa K, Namekata K, Okazawa H, Kimura H. Cystathionine beta-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS. FASEB J. 2005;19:1854–1856. [PubMed]
  • Pacheco TR, Gomes AQ, Barbosa-Morais NL, Benes V, Ansorge W, Wollerton M, Smith CW, Valcarcel J, Carmo-Fonseca M. Diversity of vertebrate splicing factor U2AF35: identification of alternatively spliced U2AF1 mRNAS. J Biol Chem. 2004;279:27039–27049. doi: 10.1074/jbc.M402136200. [PubMed] [Cross Ref]
  • Brannvall K, Hjelm H, Korhonen L, Lahtinen U, Lehesjoki AE, Lindholm D. Cystatin-B is expressed by neural stem cells and by differentiated neurons and astrocytes. Biochem Biophys Res Commun. 2003;308:369–374. doi: 10.1016/S0006-291X(03)01386-X. [PubMed] [Cross Ref]
  • Jansen E, Meulemans SM, Orlans IC, Van de Ven WJ. The NNP-1 gene (D21S2056E), which encodes a novel nuclear protein, maps in close proximity to the cystatin B gene within the EPM1 and APECED critical region on 21q22.3. Genomics. 1997;42:336–341. doi: 10.1006/geno.1997.4755. [PubMed] [Cross Ref]
  • Lu B, Jiang YJ, Zhou Y, Xu FY, Hatch GM, Choy PC. Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARalpha in murine heart. Biochem J. 2005;385:469–477. doi: 10.1042/BJ20041348. [PubMed] [Cross Ref]
  • Yamakawa K, Gao DQ, Korenberg JR. A periodic tryptophan protein 2 gene homologue (PWP2H) in the candidate region of progressive myoclonus epilepsy on 21q22.3. Cytogenet Cell Genet. 1996;74:140–145. doi: 10.1159/000134402. [PubMed] [Cross Ref]
  • Levanon D, Danciger E, Dafni N, Bernstein Y, Elson A, Moens W, Brandeis M, Groner Y. The primary structure of human liver type phosphofructokinase and its comparison with other types of PFK. DNA. 1989;8:733–743. doi: 10.1089/dna.1989.8.733. [PubMed] [Cross Ref]
  • Nagamine K, Kudoh J, Minoshima S, Kawasaki K, Asakawa S, Ito F, Shimizu N. Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain. Genomics. 1998;54:124–131. doi: 10.1006/geno.1998.5551. [PubMed] [Cross Ref]
  • Uemura T, Kudoh J, Noda S, Kanba S, Shimizu N. Characterization of human and mouse TRPM2 genes: identification of a novel N-terminal truncated protein specifically expressed in human striatum. Biochem Biophys Res Commun. 2005;328:1232–1243. doi: 10.1016/j.bbrc.2005.01.086. [PubMed] [Cross Ref]
  • Fonfria E, Murdock PR, Cusdin FS, Benham CD, Kelsell RE, McNulty S. Tissue distribution profiles of the human TRPM cation channel family. J Recept Signal Transduct Res. 2006;26:159–178. doi: 10.1080/10799890600637506. [PubMed] [Cross Ref]
  • Hill K, Tigue NJ, Kelsell RE, Benham CD, McNulty S, Schaefer M, Randall AD. Characterisation of recombinant rat TRPM2 and a TRPM2-like conductance in cultured rat striatal neurones. Neuropharmacology. 2006;50:89–97. doi: 10.1016/j.neuropharm.2005.08.021. [PubMed] [Cross Ref]
  • Boelaert K, Tannahill LA, Bulmer JN, Kachilele S, Chan SY, Kim D, Gittoes NJ, Franklyn JA, Kilby MD, McCabe CJ. A potential role for PTTG/securin in the developing human fetal brain. FASEB J. 2003;17:1631–1639. doi: 10.1096/fj.02-0948com. [PubMed] [Cross Ref]
  • Melcher T, Maas S, Herb A, Sprengel R, Higuchi M, Seeburg PH. RED2, a brain-specific member of the RNA-specific adenosine deaminase family. J Biol Chem. 1996;271:31795–31798. doi: 10.1074/jbc.271.21.12221. [PubMed] [Cross Ref]
  • Gerber A, O'Connell MA, Keller W. Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by the insertion of an Alu cassette. RNA. 1997;3:453–463. [PubMed]
  • O'Connell MA, Gerber A, Keller W. Purification of human double-stranded RNA-specific editase 1 (hRED1) involved in editing of brain glutamate receptor B pre-mRNA. J Biol Chem. 1997;272:473–478. doi: 10.1074/jbc.272.1.473. [PubMed] [Cross Ref]
  • Mittaz L, Scott HS, Rossier C, Seeburg PH, Higuchi M, Antonarakis SE. Cloning of a human RNA editing deaminase (ADARB1) of glutamate receptors that maps to chromosome 21q22.3. Genomics. 1997;41:210–217. doi: 10.1006/geno.1997.4655. [PubMed] [Cross Ref]
  • Cheon MS, Bajo M, Kim SH, Claudio JO, Stewart AK, Patterson D, Kruger WD, Kondoh H, Lubec G. Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: challenging the gene dosage effect hypothesis (Part II) Amino Acids. 2003;24:119–125. [PubMed]
  • Hagiwara H, Tajika Y, Matsuzaki T, Suzuki T, Aoki T, Takata K. Localization of Golgi 58 K protein (formiminotransferase cyclodeaminase) to the centrosome. Histochem Cell Biol. 2006;126:251–259. doi: 10.1007/s00418-006-0166-5. [PubMed] [Cross Ref]
  • Vives V, Alonso G, Solal AC, Joubert D, Legraverend C. Visualization of S100B-positive neurons and glia in the central nervous system of EGFP transgenic mice. J Comp Neurol. 2003;457:404–419. doi: 10.1002/cne.10552. [PubMed] [Cross Ref]
  • Scott HS, Antonarakis SE, Lalioti MD, Rossier C, Silver PA, Henry MF. Identification and characterization of two putative human arginine methyltransferases (HRMT1L1 and HRMT1L2) Genomics. 1998;48:330–340. doi: 10.1006/geno.1997.5190. [PubMed] [Cross Ref]

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