The region responsible for stroke on chromosome 4 in the stroke-prone spontaneously hypertensive rat.
To detect genetic loci responsible for stroke susceptibility, we produced 107 male F2 progenies crossed between stroke-prone spontaneously hypertensive rats (SHRSP/Izm) and normotensive Wistar Kyoto rats (WKY/Izm) and followed them up until they developed cerebral stroke. One hundred and twenty-five simple sequence repeat (SSR) markers were analyzed in these F2 rats. Nine of 107 F2 rats suffered from macroscopically overt stroke. In these 9 rats, the segregation ratio of 3 genotypes at 6 SSR marker loci on chromosomes 2, 4, 9, and 10 was highly distorted from the expected value (the observed sp/sp:sp/wky:wky/ wky ratio was either 6:3:0 or 6:2:1, while the expected was 1:2:1, p < 0.01 by chi 2 test). Further, the brain weight was significantly heavier (p < 0.001) in the F2 rats suffering from stroke, suggesting that the brain weight was a parameter for stroke. The brain weight of F2 rats cosegregated with D4Mit19, D4Mgh7, and D4Mgh8 (p = 0.0015, 0.0014, and 0.0040 by ANOVA, respectively) on chromosome 4 supporting genetic effects of this genetic loci on the pathogenesis of cerebral stroke. Blood pressure did not cosegregate with these markers on chromosome 4. These results suggest that a region on chromosome 4, independently of hypertension, determines genetic susceptibility to cerebral stroke.
Ikeda
K
K
Otsuka Department of International Preventive Nutritional Medicine, Kyoto University, WHO Collaborating Center for Research on Primary Prevention of Cardiovascular Diseases, Japan.
Nara
Y
Y
Matumoto
C
C
Mashimo
T
T
Tamada
T
T
Sawamura
M
M
Nabika
T
T
Yamori
Y
Y
D000818:Animals; D001921:Brain / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000235:genetics*; D002874:Chromosome Mapping; D020022:Genetic Predisposition to Disease; D008297:Male; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY