RGD Reference Report - Right ventricular hypertrophy secondary to pulmonary hypertension is linked to rat chromosome 17: evaluation of cardiac ryanodine Ryr2 receptor as a candidate. - Rat Genome Database

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Right ventricular hypertrophy secondary to pulmonary hypertension is linked to rat chromosome 17: evaluation of cardiac ryanodine Ryr2 receptor as a candidate.

Authors: Zhao, L  Sebkhi, A  Nunez, DJ  Long, L  Haley, CS  Szpirer, J  Szpirer, C  Williams, AJ  Wilkins, MR 
Citation: Zhao L, etal., Circulation 2001 Jan 23;103(3):442-7.
RGD ID: 69699
Pubmed: PMID:11157698   (View Abstract at PubMed)

BACKGROUND: Fischer 344 (F344) rats are relatively resistant to hypoxia-induced right ventricular (RV) hypertrophy compared with the Wistar-Kyoto (WKY) strain. These 2 strains were used to examine the genetic basis for the differential response. METHODS AND RESULTS: Male F(2) offspring from an F344xWKY intercross were exposed to hypoxia (10% O(2)) for 3 weeks, and pulmonary artery pressure and cardiac chamber weights were measured. Genomic DNA was screened by use of polymorphic microsatellite markers across the whole genome (excluding the sex chromosomes). A quantitative trait locus (QTL) for RV weight was identified on rat chromosome 17 (lod score 6.5) that accounted for 22% of the total variance of RV weight in the F(2) population and was independent of pulmonary artery pressure. The peak was centered over marker D17Rat41, close to Chrm3, with a 1-lod support interval of 5 cM. Comparison of homologous regions in mice and humans suggested that Ryr2, the cardiac isoform of the ryanodine receptor, colocalizes with our QTL. A panel of somatic cell hybrids and fluorescence in situ hybridization mapped Ryr2 close to the gene Chrm3 within our QTL. [(3)H]Ryanodine binding to cardiac membranes from the parental strains showed a 21% reduction in B(max) in the WKY compared with the F344 strain, with no difference in K:(d). CONCLUSIONS: These data provide the first demonstration of a QTL linked to the RV response to hypoxia-induced pulmonary hypertension. The Ryr2 receptor gene lies within this QTL and merits further investigation as a candidate for this differential RV response.



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Cm15  (Cardiac mass QTL 15)


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