Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-4-13
pubmed:abstractText
A region with a major effect on blood pressure (BP) is located on rat chromosome 1. We have previously isolated this region in reciprocal congenic strains (WKY.SHR-Sa and SHR.WKY-Sa) derived from a cross of the spontaneously hypertensive rat (SHR) with the Wistar-Kyoto rat (WKY) and shown that there are 2 distinct BP quantitative trait loci, BP1 and BP2, in this region. Sisa1, a congenic substrain from the SHR.WKY-Sa animals carrying an introgressed segment of 4.3Mb, contains BP1. Here, we report further dissection of BP1 by the creation of 2 new mutually exclusive congenic substrains (Sisa1a and Sisa1b) and interrogation of candidate genes by expression profiling and targeted transcript sequencing. Only 1 of the substrains (Sisa1a) continued to demonstrate a BP difference but with a reduced introgressed segment of 3Mb. Exonic sequencing of the 20 genes located in the Sisa1a region did not identify any major differences between SHR and WKY. However, microarray expression profiling of whole kidney samples and subsequent quantitative RT-PCR identified a single gene, Spon1 that exhibited significant differential expression between the WKY and SHR genotypes at both 6 and 24 weeks of age. Western blot analysis confirmed an increased level of the Spon1 gene product in SHR kidneys. Spon1 belongs to a family of genes with antiangiogenic properties. These findings justify further investigation of this novel positional candidate gene in BP control in hypertensive rat models and humans.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
992-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Genetic dissection of a blood pressure quantitative trait locus on rat chromosome 1 and gene expression analysis identifies SPON1 as a novel candidate hypertension gene.
pubmed:affiliation
Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't