Genetic characterization of early renal changes in a novel mouse model of diabetic kidney disease

Lois A Balmer; Rhiannon Whiting; Caroline Rudnicka; Linda Gallo; Karin A Jandeleit; Yan Chow; Zenia Chow; Kirsty L Richardson; Josephine M Forbes; Grant Morahan

doi:10.1016/j.kint.2019.04.031

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Genetic characterization of early renal changes in a novel mouse model of diabetic kidney disease

Journal article

Peer reviewed

Genetic characterization of early renal changes in a novel mouse model of diabetic kidney disease

Lois A Balmer, Rhiannon Whiting, Caroline Rudnicka, Linda Gallo, Karin A Jandeleit, Yan Chow, Zenia Chow, Kirsty L Richardson, Josephine M Forbes and Grant Morahan

Kidney International, Vol.96(4), pp.918-926

2019

DOI: https://doi.org/10.1016/j.kint.2019.04.031

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Abstract

mouse model

diabetes

diabetic kidney disease

alloxan

congenic mice

quantative trait loci

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.

Details

Title: Genetic characterization of early renal changes in a novel mouse model of diabetic kidney disease
Authors: Lois A Balmer (Author) - University of Western Australia
Rhiannon Whiting (Author) - University of Western Australia
Caroline Rudnicka (Author) - University of Western Australia
Linda Gallo (Author) - University of Queensland
Karin A Jandeleit (Author) - Monash University
Yan Chow (Author) - Ramsay Health Care
Zenia Chow (Author) - Northpark Private Hospital
Kirsty L Richardson (Author) - University of Western Australia
Josephine M Forbes (Author) - University of Queensland
Grant Morahan (Author) - University of Western Australia
Publication details: Kidney International, Vol.96(4), pp.918-926
Publisher: Elsevier Inc.
DOI: 10.1016/j.kint.2019.04.031
Organisation Unit: School of Health and Behavioural Sciences - Legacy; University of the Sunshine Coast, Queensland; School of Health - Biomedicine
Language: English
Record Identifier: 99620607702621
Output Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration
Web Of Science research areas: Urology & Nephrology

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