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Int J Mol Epidemiol Genet 2010;2(1):51-55.
Brief Communication
Strain differences and the role of AT1 receptor expression in anxiety
BJ Golding, ADJ Overall, PR Gard
School of Pharmacy & Biomolecular Sciences, University of Brighton, UK; Department of Basic Neuroscience, University
of Geneva, Switzerland.
Received August 26, 2010; accepted December 20, 2010; Epub December 26, 2010; published January 1, 2011
Abstract: 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 à 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. (IJMEG1008003).
Keywords: AT1 receptors, anxiety, anxiolytic, strain differences, angiotensin receptor associated protein (ATRAP), losartan
Full Text PDF
Address all correspondence to:
Dr. BJ Golding,
Department of Neuroscience
University of Geneva
Switzerland.
E-mail: bruno.golding@unige.ch
Brief Communication
Strain differences and the role of AT1 receptor expression in anxiety
BJ Golding, ADJ Overall, PR Gard
School of Pharmacy & Biomolecular Sciences, University of Brighton, UK; Department of Basic Neuroscience, University
of Geneva, Switzerland.
Received August 26, 2010; accepted December 20, 2010; Epub December 26, 2010; published January 1, 2011
Abstract: 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 à 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. (IJMEG1008003).
Keywords: AT1 receptors, anxiety, anxiolytic, strain differences, angiotensin receptor associated protein (ATRAP), losartan
Full Text PDF
Address all correspondence to:
Dr. BJ Golding,
Department of Neuroscience
University of Geneva
Switzerland.
E-mail: bruno.golding@unige.ch
