Reciprocal consomic strains to evaluate y chromosome effects.
We have previously demonstrated that the SHRSP Y chromosome contains a locus that contributes to hypertension in SHRSP/WKY F2 hybrids and that SHRSP exhibit an increased vulnerability to focal cerebral ischemia after permanent middle cerebral artery occlusion (MCAO). This increased vulnerability is inherited as a codominant trait, and a putative role for the Y chromosome has been suggested in F1 hybrids. The objective of this study was to investigate further the role of Y chromosome in blood pressure (BP) regulation and in the vulnerability to cerebral ischemia. We have constructed consomic strains by selectively replacing the Y chromosome from WKY rats with that of SHRSP, and vice versa, by using a marker-assisted breeding strategy. Permanent MCAO was carried out by electrocoagulation, with infarct volume expressed as a percentage of the ipsilateral hemisphere. Systolic blood pressure was measured by radiotelemetry during a baseline period of 5 weeks followed by a 3-week period of salt loading. We observed that the transfer of the Y chromosome from WKY onto SHRSP background significantly reduced systolic BP in consomic strains, SP.WKYGlaY(w) (n=6) versus SHRSP (n=6) (209.2+/-10.4 mm Hg versus 241.7+/-7.7 mm Hg, F=5.88, P=0.038) during the salt-loading period. In the reciprocal consomic strain, WKY.SPGlaY(s) (n=5), systolic BP was increased compared with WKY parental strain (n=6) (147.6+/-2.4 mm Hg versus 132.6+/-5.1 mm Hg, F=6.11, P=0.035) during baseline. Infarct volumes in consomic strains were not significantly different from their respective parental strain: WKY.SPGlaY(s) (n=7) versus WKY (n=7), 22.8+/-3.7% versus 22.2+/-8.0%, 95% CI=-12.7, 4.2, P=0.3; SP.WKYGlaY(w) (n=7) versus SHRSP (n=6), 37.7+/-4.4% versus 33.6+/-7.6%, 95% CI=-20.3, 12.1, P=0.5. We conclude that the SHRSP Y chromosome harbors a locus contributing to systolic BP, whereas no contribution to vulnerability to cerebral ischemia can be detected.
Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, and Wellcome Surgical Institute University of Glasgow, United Kingdom.
C D
CD
Negrín
M W
MW
McBride
H V
HV
Carswell
D
D
Graham
F J
FJ
Carr
J S
JS
Clark
B
B
Jeffs
N H
NH
Anderson
I M
IM
Macrae
A F
AF
Dominiczak
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight; D003433:Crosses, Genetic; D004564:Electrocoagulation; D005819:Genetic Markers; D020244:Infarction, Middle Cerebral Artery / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014998:Y Chromosome / Q000235:genetics / Q000502:physiology*
D005819:Genetic Markers