Strain differences and the role of AT1 receptor expression in anxiety

International Journal of Molecular Epidemiology and Genetics

Bruno J Golding¹  Andrew DJ Overall¹  Paul R Gard¹ 

关键词: AT1 receptors;    anxiety;    anxiolytic;    strain differences;    angiotensin receptor associated protein (ATRAP);    losartan;   

DOI  :  

学科分类：流行病学

来源: e-Century Publishing Corporation

【 摘 要 】

This study investigated strain specific differences to the anxiolytic response to losartan focusing on genetic variation that may influence such responses. This included: AT₁ receptor sequence variation, angiotensin II receptor associated protein (ATRAP) and receptor expression between strains. Sequencing of exon 3 of AT_1aR revealed no differences between BKW mice (n=6) and C57 and DBA₂ strains (n=3). Comparisons of AT¹ expression do show significant differences, whereby BKW mice showed the highest levels of expression and DBA₂ mice intermediate levels when compared to the C57 strain. Sequencing of sections of the Angiotensin receptor associated protein (ATRAP) identified a non-synonymous point mutation- (T/C) transversion (position 109-161) (SNP id = rs13467517) resulting in a Valine → Alanine (V157A) amino acid change in the BKW and DBA₂ strains. Our results indicate that the previously reported strain dependent effects are not due to variation in AT_1a receptor sequence. Differences in AT₁gene expression levels between strains, which mirror their anxiety phenotype, are observed. This is coupled with a non-synonymous single nucleotide polymorphism in ATRAP, a negative regulator of AT₁ signalling.

【 授权许可】

Unknown