Strain differences and the role of AT1 receptor expression in anxiety

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 AT1 gene expression levels between strains, which mirror their anxiety phenotype, are observed. This is coupled with a nonsynonymous single nucleotide polymorphism in ATRAP, a negative regulator of AT1 signalling.