In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 103, No. 3 ( 2001-01-23), p. 442-447
Abstract:
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 F344×WKY 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.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.103.3.442
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2001
detail.hit.zdb_id:
1466401-X
