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Genetic characterization of early renal changes in a novel mouse model of diabetic kidney disease
- Source :
- Kidney International. 96:918-926
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Genetic factors influence susceptibility to diabetic kidney disease. Here we mapped genes mediating renal hypertrophic changes in response to diabetes. A survey of 15 mouse strains identified variation in diabetic kidney hypertrophy. Strains with greater (FVB/N(FVB)) and lesser (C57BL/6 (B6)) responses were crossed and diabetic F2 progeny were characterized. Kidney weights of diabetic F2 mice were broadly distributed. Quantitative trait locus analyses revealed diabetic mice with kidney weights in the upper quartile shared alleles on chromosomes (chr) 6 and 12; these loci were designated as Diabetic kidney hypertrophy (Dkh)-1 and -2. To confirm these loci, reciprocal congenic mice were generated with defined FVB chromosome segments on the B6 strain background (B6.Dkh1/2f) or vice versa (FVB.Dkh1/2b). Diabetic mice of the B6.Dkh1/2f congenic strain developed diabetic kidney hypertrophy, while the reciprocal FVB.Dkh1/2b congenic strain was protected. The chr6 locus contained the candidate gene; Ark1b3, coding aldose reductase; the FVB allele has a missense mutation in this gene. Microarray analysis identified differentially expressed genes between diabetic B6 and FVB mice. Thus, since the two loci identified by quantitative trait locus mapping are syntenic with regions identified for human diabetic kidney disease, the congenic strains we describe provide a valuable new resource to study diabetic kidney disease and test agents that may prevent it.
- Subjects :
- Male
0301 basic medicine
Candidate gene
Quantitative Trait Loci
Mutation, Missense
030232 urology & nephrology
Congenic
Locus (genetics)
Biology
Quantitative trait locus
Kidney
Diabetes Mellitus, Experimental
Mice
Mice, Congenic
03 medical and health sciences
0302 clinical medicine
Aldehyde Reductase
Diabetes mellitus
Alloxan
medicine
Animals
Humans
Diabetic Nephropathies
Allele
Genetics
Hypertrophy
Diabetic retinopathy
medicine.disease
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Nephrology
Female
Subjects
Details
- ISSN :
- 00852538
- Volume :
- 96
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....94af51e8f7d6f0ac3a569736f787a5d1