MUTATION OF LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR GENE IS ASSOCIATED WITH THE HYPERTENSIVE PHENOTYPE IN SPONTANEOUSLY HYPERTENSIVE INBRED RAT STRAINS

We previously reported a missense mutation in the low affinity nerve g rowth factor receptor (LNGFR) gene of spontaneously hypertensive rats (SHR), proposing this gene as a promising candidate in genetic hyperte nsion. In this study we provide further support for implicating this g ene in genetic hypertension using two new inbred strains, WKHT and WKH A rats. These strains originated from crossbreeding SHR rats with norm otensive Wistar-Kyoto rats (WKY): WKHT rats are hypertensive but not h yperactive, and WKHA rats are hyperactive but not hypertensive. Nucleo tide sequence analysis of the LNGFR gene revealed that WKHT has the sa me mutation as SHR, whereas WKHA has the normal sequence, as seen in W KY. These results support our original hypothesis that the mutated LNG FR gene is linked to hypertension, since the mutation had co-segregate d with the hypertensive trait, and not hyperactivity trait of SHR.