Increased renal hypertrophy in diabetic mice genetically modified at the haptoglobin locus.
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.
Miller-Lotan
Rachel
R
Technion Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Herskowitz
Yehuda
Y
Kalet-Litman
Shiri
S
Nakhoul
Farid
F
Aronson
Doron
D
Zoabi
Roaa
R
Asaf
Roy
R
Ben-Izhak
Ofer
O
Sabo
Edmond
E
Lim
Sai-Kiang
SK
Baumann
Heinz
H
Berger
Franklin G
FG
Levy
Andrew P
AP
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000235:genetics*; D008040:Genetic Linkage; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D006984:Hypertrophy; D007668:Kidney / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout
D006242:Haptoglobins