title: Increased renal hypertrophy in diabetic mice genetically modified at the haptoglobin locus.
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.
authors.affiliation: Technion Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Miller-Lotan
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Herskowitz
authors.forename: Shiri
authors.initials: S
authors.lastname: Kalet-Litman
authors.forename: Farid
authors.initials: F
authors.lastname: Nakhoul
authors.forename: Doron
authors.initials: D
authors.lastname: Aronson
authors.forename: Roaa
authors.initials: R
authors.lastname: Zoabi
authors.forename: Roy
authors.initials: R
authors.lastname: Asaf
authors.forename: Ofer
authors.initials: O
authors.lastname: Ben-Izhak
authors.forename: Edmond
authors.initials: E
authors.lastname: Sabo
authors.forename: Sai-Kiang
authors.initials: SK
authors.lastname: Lim
authors.forename: Heinz
authors.initials: H
authors.lastname: Baumann
authors.forename: Franklin G
authors.initials: FG
authors.lastname: Berger
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Levy
mesh_terms: 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
chemical_list: D006242:Haptoglobins