Strain differences and the role of AT1 receptor expression in anxiety

International Journal of Molecular Epidemiology and Genetics

Bruno J Golding¹ 

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 AT1aR 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 AT1a 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】

CC BY-NC