| Popis: |
Hypertension is a growing problem in the United States, exerting a great toll on the national health and economy. The Rattus norvegicus Spontaneously Hypertensive Rat (SHR) strain has been the preferred physiological model for the study of essential hypertension for decades. Both humans and rats show a pattern of Y chromosome linked hypertension, consistent with a conserved Y chromosome hypertensive locus in mammals. The Y chromosome gene, Sry has long been known for testis determination in mammals, but transcription in adult male tissues and reported effects on regulatory pathways makes Sry a candidate gene for the Y chromosome hypertensive locus. While most mammals have a single Sry locus on the Y chromosome, several rodent species have been shown to have multiple loci. Previously, six divergent loci of Sry had been identified in The University of Akron’s SHR (SHR/Akr) strain, with full coding region and conserved reading frame, but differing by SNPs and insertions/deletions. Here, sequence data of Sry loci was expanded to include more flanking sequence in SHR/Akr and three additional rat strains, with the intent of identifying hypertensive sequence variants in SHR/Akr. The University of Akron’s Wistar Kyoto (WKY/Akr) strain and Charles River Labs SHR (SHR/crl) strain are closely related strains, which both possess a normotensive Y chromosome. Harlan Sprague Dawley’s Sprague Dawley (SD/hsd) strain is an unrelated strain with a normotensive Y chromosome. Sequence data was determined from the sequencing of clones produced from amplified genomic DNA as well as direct sequencing of PCR products. In addition to the coding region, nearly 400bp of 5’ flanking, and 1200bp of 3’ flanking regions were sequenced, from each strain. All strains possess six shared Sry loci. These six loci are identical in SHR/Akr, WKY/Akr, and SHR/crl strains. Minor SNP differences in were found in SD/hsd, consistent with a more distant relationship from the other strains. An additional Sry locus, Sry3, was only found only in the SHR strains. Sequence differences in Sry3 between the SHR/Akr and SHR/crl strains are consistent with the observed differences in Y chromosome hypertension. This suggests that Sry3 is responsible for Y chromosome hypertension. |
