1. Candidate Agtr2 influenced genes and pathways identified by expression profiling in the developing brain of Agtr2(-/y) mice
- Author
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John G. Archie, Anand K. Srivastava, Chun-Huai Cheng, Silvia Heringer-Walther, Thomas Walther, Traci L. Pawlowski, and Chin-Fu Chen
- Subjects
Male ,Candidate gene ,Dendritic spine ,Central nervous system ,Population ,Intellectual disability ,Biology ,Receptor, Angiotensin, Type 2 ,Article ,Learning and memory ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Gene expression ,Genetics ,medicine ,Animals ,RNA, Messenger ,education ,Gene ,Expression profiling ,030304 developmental biology ,Oligonucleotide Array Sequence Analysis ,Mice, Knockout ,0303 health sciences ,education.field_of_study ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Brain ,Gene Expression Regulation, Developmental ,Cell biology ,Gene expression profiling ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Agtr2 ,Female ,Signal transduction ,030217 neurology & neurosurgery ,Biomarkers ,Signal Transduction - Abstract
Intellectual disability (ID) is a common developmental disability observed in 1 to 3% 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.
- Published
- 2009