Quantitative Trait Loci (QTLs) were found in a population of male F2 animals derived from an SHR(LJ)x WKY(LJ) cross for a number of phenotypic traits regulated by renal function. One QTL (LOD=4.45) is located on chromosome #7 and is associated with a lower plasma ionized calcium concentration in SHR. A second QTL (LOD greater than 3.40), located on chromosome #2, is associated with increased urinary excretion of calcium in the SHR. This QTL is the only one related to renal excretion that is present when the excretion data are normalized both per unit of excreted creatinine and as amount excreted per body weight. We consider these two calcium-related traits as traits most likely to yield information in studies of SHR-WKY congenics. Therefore, congenic strains of animals containing the relevant chromosome segments from SHR chromosomes #2 or #7 will be placed on a WKY background and the reciprocal congenics developed. These congenic strains will be raised after weaning on one of two diets, a low (0.3% Ca) or high (1.9% Ca) calcium diet traditionally used in this program. All animals will be studied for blood pressure, plasma ionized Ca&Mg, Na, K & Cl; for urinary excretion of creatinine and of Ca, Na, K and Cl; and for renal thiazide receptor density. These QTLs were identified by genomic scanning of a limited number of the male f2 animals on whom these renal traits have been determined. We will continue collaborative efforts with Core C, Molecular Genetics, in order to identify additional QTLs predicted to be present by the patterns of inheritance we found in this population. In addition, this application requests support for the initiation of genotyping of the DNA from a large population of female F2 animals on whom these renal traits have already determined. Since the difference between SHR and WKY for several of these traits are greater in females than males, there is enhanced likelihood that QTLs of major interest for these traits will be detected. Completion of these proposed studies will provide a most rigorous test of the postulates (a) that alterations in calcium homeostasis are of importance in the regulations (1) of blood pressure, in both """"""""permissive"""""""" and """"""""non- permissive"""""""" genetic backgrounds and (2) of the renal thiazide receptor, and (b) that genes modulating renal function can be identified by this genetic paradigm.
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