1. J Am Soc Nephrol. 2003 Jul;14(7):1844-50.
Quantitative trait loci for hypercalciuria in a rat model of kidney stone
disease.
Hoopes RR Jr(1), Reid R, Sen S, Szpirer C, Dixon P, Pannett AA, Thakker RV,
Bushinsky DA, Scheinman SJ.
Author information:
(1)Department of Medicine, State University of New York Upstate Medical
University, 750 East Adams Street, Syracuse, NY 13210, USA.
Hypercalciuria is the most common risk factor for kidney stones and has a
recognized familial component. The genetic hypercalciuric stone-forming (GHS) rat
is an animal model that closely resembles human idiopathic hypercalciuria, with
excessive intestinal calcium absorption, increased bone resorption, and impaired
renal calcium reabsorption; overexpression of the vitamin D receptor (VDR) in
target tissues; and calcium nephrolithiasis. For identifying genetic loci that
contribute to hypercalciuria in the GHS rat, an F2 generation of 156 rats bred
from GHS female rats and normocalciuric WKY male rats was studied. The calcium
excretion was six- to eightfold higher in the GHS female than in the WKY male
progenitors. Selective genotyping of those F2 rats with the highest 30% and
lowest 30% rates of calcium excretion was performed, scoring 98 markers with a
mean interval of 23 cM across all 20 autosomes and the X chromosome. With the use
of strict criteria for significance, significant linkage was found between
hypercalciuria and a region of chromosome 1 at D1Rat169 (LOD, 2.91). Suggestive
linkage to regions of chromosomes 4, 7, 10, and 14 was found. The proportion of
phenotypic variance contributed by the region on chromosome 1, with appropriate
adjustments, was estimated to be 7%. Candidate genes encoding the VDR and the
calcium-sensing receptor were localized to regions on rat chromosomes 7 and 11,
respectively, but the suggestive quantitative trait locus on chromosome 7 was not
in the region of the VDR gene locus. Identification of genes that contribute to
hypercalciuria in this animal model should prove valuable in understanding
idiopathic hypercalciuria and kidney stone disease in humans.
PMID: 12819244 [PubMed - indexed for MEDLINE]
PUBMED: 12819244
Find other GeneSets from this publication
GeneWeaver