A major X-linked locus affects kidney function in mice.
Document Type
Article
Publication Date
12-1-2012
JAX Source
Mol Genet Genomics 2012 Dec; 287(11-12):845-54.
PMID
23011808
Volume
287
Issue
11-12
First Page
845
Last Page
854
ISSN
1617-4623
Abstract
Chronic kidney disease is a common disease with increasing prevalence in the western population. One common reason for chronic kidney failure is diabetic nephropathy. Diabetic nephropathy and hyperglycemia are characteristics of the mouse inbred strain KK/HlJ, which is predominantly used as a model for metabolic syndrome due to its inherited glucose intolerance and insulin resistance. We used KK/HlJ, an albuminuria-sensitive strain, and C57BL/6J, an albuminuria-resistant strain, to perform a quantitative trait locus (QTL) cross to identify the genetic basis for chronic kidney failure. Albumin-creatinine ratio (ACR) was measured in 130 F2 male offspring. One significant QTL was identified on chromosome (Chr) X and four suggestive QTL were found on Chrs 6, 7, 12, and 13. Narrowing of the QTL region was focused on the X-linked QTL and performed by incorporating genotype and expression analyses for genes located in the region. From the 485 genes identified in the X-linked QTL region, a few candidate genes were identified using a combination of bioinformatic evidence based on genomic comparison of the parental strains and known function in urine homeostasis. Finally, this study demonstrates the significance of the X chromosome in the genetic determination of albuminuria.
Recommended Citation
Leduc M,
Savage H,
Stearns T,
Cario C,
Walsh K,
Paigen B,
Berndt A.
A major X-linked locus affects kidney function in mice. Mol Genet Genomics 2012 Dec; 287(11-12):845-54.