1. Hypertension. 2003 Dec;42(6):1191-7. Epub 2003 Nov 17.
Isolation of a chromosome 1 region affecting blood pressure and vascular disease
traits in the stroke-prone rat model.
Kato N(1), Nabika T, Liang YQ, Mashimo T, Inomata H, Watanabe T, Yanai K, Yamori
Y, Yazaki Y, Sasazuki T.
Author information:
(1)Department of Gene Diagnostics and Therapeutics, Research Institute,
International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo
162-8655, Japan. nokato@ri.imcj.go.jp
Recently, a genome-wide screen has shown a major quantitative trait locus (QTL)
for a stroke-associated phenotype on rat chromosome 1 (RNO1) independent of QTL
for blood pressure (BP) in the stroke-prone spontaneously hypertensive rat
(SHRSP) of a Heidelberg colony. However, it remains to be elucidated whether
these observations reflect the existence of different genes predisposing to each
of the disorders. To address this issue, we performed comprehensive approaches in
a Japanese colony, Izm, as follows. First, we undertook genome-wide searches in
F1(SHRSP/IzmxWKY/Izm)xSHRSP/Izm back-cross (n=63) to pursue a causal relation
between hypertension and stroke. Although the strongest linkage to BP (LOD score
of 3.4) was identified on RNO1, its relevance to stroke was not supported in the
F1 back-cross studied. Second, we also investigated linkage to BP in F2 progeny
(n=175) involving the stroke-resistant (or normal) spontaneously hypertensive rat
(SHR). In F2 studies of SHR/Izm, this locus did not appear to constitute a
principal BP QTL. Third, we constructed congenic animals with detailed phenotype
characterization. Transfer of a chromosomal fragment between markers Klk1 and
D1Rat116 from WKY/Izm onto the SHRSP/Izm background lowered systolic BP by 20 to
80 mm Hg, prevented development of apparent stroke, and exaggerated impaired
glucose tolerance. In conclusion, we have successfully isolated an RNO1 region
affecting BP, stroke, and glucose tolerance in SHRSP/Izm-derived congenic rats.
The size of the introgressed region is large, but our novel congenic strain
should help delineate complex, genetic impairments underlying BP and associated
vascular disease phenotypes.
PMID: 14623828 [PubMed - indexed for MEDLINE]
PUBMED: 14623828
Find other GeneSets from this publication
GeneWeaver