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Increased renal hypertrophy in diabetic mice genetically modified at the haptoglobin locus
Author(s) -
MillerLotan Rachel,
Herskowitz Yehuda,
KaletLitman Shiri,
Nakhoul Farid,
Aronson Doron,
Zoabi Roaa,
Asaf Roy,
BenIzhak Ofer,
Sabo Edmond,
Lim SaiKiang,
Baumann Heinz,
Berger Franklin G.,
Levy Andrew P.
Publication year - 2005
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.556
Subject(s) - medicine , endocrinology , allele , haptoglobin , diabetes mellitus , genotype , type 2 diabetes , renal hypertrophy , biology , muscle hypertrophy , diabetic nephropathy , gene , genetics
Background The human haptoglobin ( Hp ) gene is polymorphic with two functional classes of alleles, denoted 1 and 2. We have demonstrated in three longitudinal studies and several cross‐sectional studies that the Hp genotype is an independent risk factor for diabetic vascular disease. These studies have presented a compelling argument that diabetic individuals homozygous for the Hp 1 allele are at decreased risk of vascular complications as compared to diabetic individuals with the Hp 2 allele. Methods The naturally occurring (wild type) mouse Hp is a class 1 Hp allele. We examined renal hypertrophy in wild‐type mice, Hp knockout mice (Hp 0), and in mice with the Hp 2 allele (Hp 2) with and without diabetes. Results In the absence of diabetes, we found that renal hypertrophy was significantly increased in Hp 0 mice and that this could be prevented with vitamin E. There was no difference between wild type and Hp 2 mice with regard to renal hypertrophy in the absence of diabetes. However, in the presence of diabetes, Hp 2 mice demonstrated a significant increase in renal hypertrophy as compared to wild‐type mice. Conclusions These results support a direct linkage between diabetic vascular disease and the Hp genotype. These Hp‐modified mice may serve as a platform on which to test a variety of pharmacological agents in order to decrease diabetic vascular disease. Copyright © 2005 John Wiley & Sons, Ltd.