Review Article

Increased renal hypertrophy in diabetic mice genetically modified at the haptoglobin locus

  1. Rachel Miller-Lotan1,
  2. Yehuda Herskowitz1,
  3. Shiri Kalet-Litman1,
  4. Farid Nakhoul2,
  5. Doron Aronson3,
  6. Roaa Zoabi1,
  7. Roy Asaf1,
  8. Ofer Ben-Izhak4,
  9. Edmond Sabo5,
  10. Sai-Kiang Lim6,
  11. Heinz Baumann7,
  12. Franklin G. Berger8,
  13. Andrew P. Levy1,*

Article first published online: 26 APR 2005

DOI: 10.1002/dmrr.556

Issue

Diabetes/Metabolism Research and Reviews

Diabetes/Metabolism Research and Reviews

Volume 21, Issue 4, pages 332–337, July/August 2005

Additional Information

How to Cite

Miller-Lotan, R., Herskowitz, Y., Kalet-Litman, S., Nakhoul, F., Aronson, D., Zoabi, R., Asaf, R., Ben-Izhak, O., Sabo, E., Lim, S.-K., Baumann, H., Berger, F. G. and Levy, A. P. (2005), Increased renal hypertrophy in diabetic mice genetically modified at the haptoglobin locus. Diabetes/Metabolism Research and Reviews, 21: 332–337. doi: 10.1002/dmrr.556

Author Information

  1. 1

    Technion Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

  2. 2

    Department of Nephrology, Rambam Medical Center, Haifa, Israel

  3. 3

    Department of Cardiology, Rambam Medical Center, Haifa, Israel

  4. 4

    Department of Pathology, Rambam Medical Center, Haifa, Israel

  5. 5

    Department of Pathology, Carmel Medical Center, Haifa, Israel

  6. 6

    The National University Medical Institutes, Singapore, Singapore

  7. 7

    Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York, USA

  8. 8

    Department of Biological Sciences, University of South Carolina, Columbia, South Carolina, USA

*Technion Faculty of Medicine, POB 9649, Haifa 31096, Israel.

Publication History

  1. Issue published online: 15 JUN 2005
  2. Article first published online: 26 APR 2005
  3. Manuscript Accepted: 17 FEB 2005
  4. Manuscript Revised: 19 JAN 2005
  5. Manuscript Received: 3 JUN 2004

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (99K)

Keywords:

  • diabetic vascular complications;
  • genetic susceptibility;
  • haptoglobin;
  • hemoglobin

Abstract

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.

View Full Article (HTML) Get PDF (99K)