MAPPING GENES-CONTROLLING HEMATOCRIT IN THE SPONTANEOUSLY HYPERTENSIVE RAT

The genes that determine the baseline hematocrit level in humans and e xperimental animals are unknown. The spontaneously hypertensive rat (S HR), the most widely used animal model of human essential hypertension , exhibits an increased hematocrit when compared with the normotensive Brown Norway (BN-Lx) strain (0.54 +/- 0.02 vs. 0.44 +/- 0.02, p < 0.0 1). Distribution of hematocrit values among recombinant inbred (RI) st rains derived from SHR and BN-Lx progenitors was continuous, which sug gests a polygenic mode of inheritance. The narrow heritability of the hematocrit was estimated to be 0.32. The Eno2 marker on Chromosome (Ch r) 4 showed the strongest association (p < 0.0001) with the observed v ariability of hematocrit among RI strains. The erythropoietin (Epo) ge ne, originally reported to be syntenic with Eno2, has been mapped to C hr 12, thus excluding it as a potential candidate gene for the increas ed hematocrit in the SHR. The current linkage data extend homologies b etween rat, mouse, and human chromosomes.