Phenotypic selection: A successful strategy to fix major genes of hypertension

Hypertension is dominantly inherited in cross hybrids between hypertensive SHR/Mol and normotensive BB/OK rats. We used these cross hybrids for repeat ed backcrossing of selected hypertensive animals onto normotensive BB/OK ra ts to flu high blood pressure and to generate a hypertensive and diabetic B B/OK rat subline. After 8 backcrosses, the backcross parents were genetical ly analysed with the aid of 259 microsatellite markers to identify SHR gene s causing blood pressure of 177 +/- 10 mmHg in this BB/OK rat subline. Loci on chromosomes 1, 14 and 18 showed longest heterozygosity. These loci migh t contain major genes of the SHR rat causing hypertension in this BB/OK rat subline. This classical strategy seems to be most suitable to fix major ge nes of hypertension in particular and complex traits in general and therefo re to generate new animal models.