Genetic basis of salt-susceptibility in the Sabra rat model of hypertension.
The Sabra salt-sensitive SBH/y and salt-resistant SBN/y rats constitute a unique experimental model of hypertension in which salt-susceptibility is genetically determined and expressed only after salt-loading, without the development of spontaneous hypertension. To determine the genetic basis of salt-susceptibility in the Sabra rats, the candidate gene and total genome screen approaches were adopted. The likely candidate genes in this model incorporate salt-related physiological mechanisms such as the nitric oxide system, the arginine vasopressin axis and the epithelial sodium channel. In the random genome search scheme for culprit genes, SBH/y and SBN/y were cross-bred. A highly unusual and composite mode of transmission of salt-susceptibility was found in this cross, emphasizing the complexity of the genetic basis of salt-susceptibility. Linkage analysis of the entire rat genome with a large number of widely distributed microsatellite markers identified three putative gene loci on chromosomes 1 and 17 that contribute importantly to salt-sensitivity and/or resistance, and uncovered sex specificity in the role that salt-susceptibility genes fulfill in the development of hypertension.
Yagil
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Laboratory for Molecular Medicine, Barzilai Medical Center, Ashkelon, Israel. labmomed@bgumail.bgu.ac.il
Yagil
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D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics*; D012965:Sodium Chloride / Q000494:pharmacology*
D012965:Sodium Chloride