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Archie, John G. (2)
Chen, Chin-Fu (1)
Cheng, Chun-Huai (1)
Heringer-Walther, Silvia (1)
Karplus, Kevin (1)
Paluszewski, Martin (1)
Pawlowski, Traci L. (1)
Srivastava, Anand K. (1)
Walther, Thomas (1)
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Candidate Agtr2 influenced genes and pathways identified by expression profiling in the developing brain of Agtr2−/y mice
Pawlowski, Traci L.
Srivastava, Anand K.
Intellectual disability (ID) is a common developmental disability observed in one to three percent of the human population. A possible role for the Angiotensin II type 2 receptor (AGTR2) in brain function, affecting learning, memory, and behavior, has been suggested in humans and rodents. Mice lacking the Agtr2 gene (Agtr2−/y) showed significant impairment in their spatial memory and exhibited abnormal dendritic spine morphology. To identify Agtr2 influenced genes and pathways, we performed whole genome microarray analysis on RNA isolated from brains of Agtr2−/y and control male mice at embryonic day 15 (E15) and postnatal day one (P1). The gene expression profiles of the Agtr2−/y brain samples were significantly different when compared to profiles of the age-matched control brains. We identified 62 differently expressed genes (p ≤ 0.005) at E15 and in P1 brains of the Agtr2−/y mice. We verified the differential expression of several of these genes in brain samples using quantitative RT-PCR. Differentially expressed genes encode molecules involved in multiple cellular processes including microtubule functions associated with dendritic spine morphology. This study provides insight into Agtr2 influenced candidate genes and suggests that expression dysregulation of these genes may modulate Agtr2 actions in the brain that influences learning and memory.
Learning and memory; Intellectual Disability; Dendritic spine; Expression profiling; Agtr2
Applying Undertaker to Quality Assessment
Our group tested three quality assessment functions in CASP8: a function which used only distance constraints derived from alignments (SAM-T08-MQAO), a function which added other single-model terms to the distance constraints (SAM-T08-MQAU), and a function which used both single-model and consensus terms (SAM-T08-MQAC).
We analyzed the functions both for ranking models for a single target and for producing an accurate estimate of GDT_TS. Our functions were optimized for the ranking problem, so are perhaps more appropriate for metaserver applications than for providing a trustworthiness estimate for single models.
On the CASP8 test, the functions with more terms performed better. The MQAC consensus method was substantially better than either single-model function, and the MQAU function was substantially better than the MQAO function that used only constraints from alignments.
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