Genetic Analysis of Obesity-Induced Diabetic Nephropathy in BTBR Mice.
Diabetes
; 73(2): 312-317, 2024 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-37935024
ABSTRACT
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in the U.S. and has a significant impact on human suffering. Leptin-deficient BTBR (BTBRob/ob) mice develop hallmark features of obesity-induced DN, whereas leptin-deficient C57BL/6J (B6ob/ob) mice do not. To identify genetic loci that underlie this strain difference, we constructed an F2 intercross between BTBRob/ob and B6ob/ob mice. We isolated kidneys from 460 F2 mice and histologically scored them for percent mesangial matrix and glomerular volume (â¼50 glomeruli per mouse), yielding â¼45,000 distinct measures in total. The same histological measurements were made in kidneys from B6 and BTBR mice, either lean or obese (Lepob/ob), at 4 and 10 weeks of age, allowing us to assess the contribution of strain, age, and obesity to glomerular pathology. All F2 mice were genotyped for â¼5,000 single nucleotide polymorphisms (SNPs), â¼2,000 of which were polymorphic between B6 and BTBR, enabling us to identify a quantitative trait locus (QTL) on chromosome 7, with a peak at â¼30 Mbp, for percent mesangial matrix, glomerular volume, and mesangial volume. The podocyte-specific gene nephrin (Nphs1) is physically located at the QTL and contains high-impact SNPs in BTBR, including several missense variants within the extracellular immunoglobulin-like domains.
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Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Nefropatias Diabéticas
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article