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

Spontaneously diabetic BB/OK rats are not genetically susceptible to develo p diabetic complications as hypertension or nephropathy. Recently, we gener ated 5 congenic BB. SHR rat strains by transferring different chromosomal r egions of the spontaneously hypertensive rat (SHR) onto the genetic backgro und of BB/OK rats. Four out of 5 strains showed a weak increase of blood pr essure (8 mmHg). This weak blood pressure effect indicated that the transfe rred regions fo not contain major genes for hypertension. That prompted us to choose the classical procedure of phenotypic selection to fix major gene s causing hypertension in a BB/OK rat subline generated by cross of BB/OK a nd SHR and repeated backcrossing of animals with highest blood pressure ont o normotensive BB/OK rats. After 7 backcrosses (N8), all backcross parents were genetically analysed with the aid of 259 microsatellites to identify l oci causing blood pressure of 177 +/- 10 mmHg in this BB/OK rat subline. Th e data revealed, that loci on chromosome 1, 14 and 18 were heterozygous unt il BC5, BC6 and BC7, respectively. Considering the relative stable high blo od pressure during the backcross procedure, these loci might be of essentia l importance for the development of hypertension in the SHR.