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1.  APOH Promoter Polymorphisms in Relation to Lupus and Lupus-Related Phenotypes 
The Journal of rheumatology  2009;36(2):315-322.
Sequence variation in gene promoters is often associated with disease risk. In this study, we tested the hypothesis that common promoter variation in the APOH gene (encoding for β2-glycoprotein I) is associated with systemic lupus erythematosus (SLE) risk and SLE-related clinical phenotypes in a Caucasian cohort.
We used a case-control design and genotyped 345 SLE women and 454 healthy control women for 8 APOH promoter single nucleotide polymorphisms (SNPs) (−1284C>G, −1219G>A, −1190G>C, −759 A>G, − 700C>A, −643T>C, −38G>A, and −32C>A). Association analyses were performed on single SNPs and haplotypes. Haplotype analyses were performed using EH (Estimate Haplotype-frequencies) and Haploview programs. In vitro reporter gene assay was performed in COS-1 cells. Electrophoretic mobility shift assay (EMSA) was performed using HepG2 nuclear cells.
Overall haplotype distribution of the APOH promoter SNPs was significantly different between cases and controls (P = 0.009). The −643C allele was found to be protective against carotid plaque formation (adjusted OR = 0.37, P = 0.013) among SLE patients. The −643C allele was associated with a ~ 2-fold decrease in promoter activity as compared to wild-type −643T allele (mean ± standard deviation: 3.94 ± 0.05 vs. 6.99 ± 0.68, P = 0.016). EMSA showed that the −643T>C SNP harbors a binding site for a nuclear factor. The −1219G>A SNP showed a significant association with the risk of lupus nephritis (age-adjusted OR = 0.36, P = 0.016).
Our data indicate that APOH promoter variants may be involved in the etiology of SLE, especially the risk for autoimmune-mediated cardiovascular disease.
PMCID: PMC2667221  PMID: 19132787
APOH; β2-glycoprotein I; promoter; SLE; lupus; polymorphism
2.  Targeted ablation and reorganization of the principal preplate neurons and their neuroblasts identified by golli promoter transgene expression in the neocortex of mice 
ASN NEURO  2009;1(4):e00018.
The present study delineates the cellular responses of dorsal pallium to targeted genetic ablation of the principal preplate neurons of the neocortex. Ganciclovir treatment during prenatal development (E11–E13; where E is embryonic day) of mice selectively killed cells with shared S-phase vulnerability and targeted expression of a GPT [golli promoter transgene, linked to HSV-TK (herpes simplex virus-thymidine kinase), τ-eGFP (τ-enhanced green fluorescent protein) and lacZ (lacZ galactosidase) reporters] localized in preplate neurons. Morphogenetic fates of attacked neurons and neuroblasts, and their successors, were assessed by multiple labelling in time-series comparisons between ablated (HSV-TK+/0) and control (HSV-TK0/0) littermates. During ablation generation, neocortical growth was suppressed, and compensatory reorganization of non-GPT ventricular zone progenitors of dorsal pallium produced replacements for killed GPT neuroblasts. Replacement and surviving GPT neuroblasts then produced replacements for killed GPT neurons. Near-normal restoration of their complement delayed the settlement of GPT neurons into the reconstituted preplate, which curtailed the outgrowth of pioneer corticofugal axons. Based on this evidence, we conclude that specific cell killing in ablated mice can eliminate a major fraction of GPT neurons, with insignificant bystander killing. Also, replacement GPT neurons in ablated mice originate exclusively by proliferation from intermediate progenitor GPT neuroblasts, whose complement is maintained by non-GPT progenitors for inductive regulation of the total complement of GPT neurons. Finally, GPT neurons in both normal and ablated mice meet all morphogenetic criteria, including the ‘outside-in’ vertical gradient of settlement, presently used to identify principal preplate neurons. In ablated mice, delayed organization of these neurons desynchronizes and isolates developing neocortex from the rest of the brain, and permanently impairs its connectivity.
PMCID: PMC2785513  PMID: 19807694
morphogenesis; neocortex; neuron; plasticity; preplate; progenitor; BrdU, bromodeoxyuridine; CSF, cerebrospinal fluid; DAB, 3,3′-diaminobenzidine; E, embryonic day; τ-eGFP, τ-enhanced green fluorescent protein; GPT, golli promoter transgene; h, counted profile thickness; HSV-TK, herpes simplex virus-thymidine kinase; i.p., intraperitoneal; lacZ, lacZ galactosidase; MAT, metaphase, anaphase and telophase; MBP, myelin basic protein; n.a., numerical aperture; P, postnatal day; Ts, section thickness; TUNEL, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling; X-gal, 5-bromo-4-chloro-3-indolyl-β-d-galactoside
3.  Targeted overexpression of a golli–myelin basic protein isoform to oligodendrocytes results in aberrant oligodendrocyte maturation and myelination 
ASN NEURO  2009;1(4):e00017.
Recently, several in vitro studies have shown that the golli–myelin basic proteins regulate Ca2+ homoeostasis in OPCs (oligodendrocyte precursor cells) and immature OLs (oligodendrocytes), and that a number of the functions of these cells are affected by cellular levels of the golli proteins. To determine the influence of golli in vivo on OL development and myelination, a transgenic mouse was generated in which the golli isoform J37 was overexpressed specifically within OLs and OPCs. The mouse, called JOE (J37-overexpressing), is severely hypomyelinated between birth and postnatal day 50. During this time, it exhibits severe intention tremors that gradually abate at later ages. After postnatal day 50, ultrastructural studies and Northern and Western blot analyses indicate that myelin accumulates in the brain, but never reaches normal levels. Several factors appear to underlie the extensive hypomyelination. In vitro and in vivo experiments indicate that golli overexpression causes a significant delay in OL maturation, with accumulation of significantly greater numbers of pre-myelinating OLs that fail to myelinate axons during the normal myelinating period. Immunohistochemical studies with cell death and myelin markers indicate that JOE OLs undergo a heightened and extended period of cell death and are unable to effectively myelinate until 2 months after birth. The results indicate that increased levels of golli in OPC/OLs delays myelination, causing significant cell death of OLs particularly in white matter tracts. The results provide in vivo evidence for a significant role of the golli proteins in the regulation of maturation of OLs and normal myelination.
PMCID: PMC2785512  PMID: 19715557
cell death; dysmyelination; golli protein; myelination; oligodendrocyte development; BDNF, brain-derived neurotrophic factor; CC, corpus callosum; ClCsp3, cleaved caspase 3; CNP, 2′,3′-cyclic nucleotide phosphodiesterase; DIV, days in vitro; FGFR, fibroblast growth factor receptor; GFAP, glial fibrillary acidic protein; GFP, green fluorescent protein; hemi, hemizygous; JOE, J37-overexpressing; MBP, myelin basic protein; MyAP, myelinated axon profile; OL, oligodendrocyte; OPC, oligodendrocyte precursor cell; P, postnatal day; PDGFRα, platelet-derived growth factor receptor α; PLP, proteolipid protein; TBS-T, Tris-buffered saline with Tween 20; WT, wild-type

Results 1-3 (3)