Insight into the genetics of diabetic nephropathy through the study of mice.
OBJECTIVE
To discuss mouse models of diabetic nephropathy and their use in discovering genetic risk factors predisposing to diabetic nephropathy.


RESULTS
Despite occurring in only 10-40% of diabetic patients, diabetic nephropathy is the largest single cause of end stage renal disease in the USA. Accumulated evidence points to critical genetic factors that predispose a subset of diabetic patients to nephropathy. Defining the genes that confer risk for nephropathy in human populations has proven challenging. The use of robust genetic reagents available in the laboratory mouse provides a complementary approach to defining genes that predispose to diabetic nephropathy in mice and humans. These findings support the existence of dominant mutations predisposing to diabetic nephropathy in mice as well as substantiating an important role for eNOS in forestalling the development of diabetic nephropathy.


CONCLUSIONS
When studied for a sufficient duration of diabetic hyperglycemia, some strains of mice exhibit changes similar to those of human diabetic nephropathy. The unique genetic reagents in mice should help accelerate the identification of genes predisposing to diabetic nephropathy.
Breyer
Matthew D
MD
Biotherapeutics Discovery Research Eli Lilly and Company, Indianapolis, Indiana 46225, USA. breyerma@lilly.com
Qi
Zhonghua
Z
Tchekneva
Elena E
EE
Harris
Raymond C
RC
D000818:Animals; D003928:Diabetic Nephropathies / Q000235:genetics*; D004195:Disease Models, Animal; D016678:Genome; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D040641:Quantitative Trait Loci