Skip to main content
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;8(3):349–358. doi: 10.1111/j.1582-4934.2004.tb00324.x

Double transgenic mice with Type 1 diabetes mellitus develop somatic, metabolic and vascular disorders

D L Radu 1,, Adriana Georgescu 2, Crina Stavaru 1, Alina Carale 2, Doina Popov 2
PMCID: PMC6740211  PMID: 15491510

Abstract

The double transgenic mice (dTg) were obtained by mating: (i) transgenic mice expressing the hemagglutinin of influenza virus under the insulin promoter with (ii) transgenic mice expressing specific T lymphocytes with receptor for the immunodominant epitope of the same virus. In this study we show that dTg mice developed type 1 diabetes mellitus associated with hyperglycemia, low level of plasma insulin, glucosuria, weight loss and ∼ 90% mortality (at 3 months biological age). The membrane of red blood cells was more sensitive to osmotic shock in diabetic mice, compared to non‐diabetic mice, assessing systemic oxidative stress. Both vasoconstriction and vasorelaxation of the renal arteries decreased significantly in diabetic mice (compared to the control group of non‐diabetic mice) related to the phenotypic change of endothelium and smooth muscle cells within the artery wall. This animal model, may be used in developing various strategies to study pancreatic β‐cell function, as well as for a better metabolic control conducting to a reduced risk of vascular complications.

Keywords: Type 1 diabetes, transgenic mice

References

  • 1. Sakaguchi S., Animal models of autoimmunity and their relevance to human diseases, Curr. Opin. Immunol., 12: 684–690, 2000. [DOI] [PubMed] [Google Scholar]
  • 2. Fujii S., Advances in the understanding of diabetic vascular disease, J. Cardiovasc. Risk, 4: 67–69, 1997. [PubMed] [Google Scholar]
  • 3. Kirberg J., Baron A., Jabob S., Rolink A., Karjalainen K., von Boehmer, H. , Thymic selection of CD8 single positive cells with a major histocompatibility complex‐restricted receptor, J. Exp. Med., 180: 25–34, 1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Degermann S., Reilly C., Scott B., Ogata L., von Boehmer, H. , Lo D., On the various manifestaitions of autoimmune diabetes in rodent animals, Eur. J. Immunol., 24: 3155–3160, 1994. [DOI] [PubMed] [Google Scholar]
  • 5. Radu D.L., Brumeanu T. D., McEvoy R.C., Bona C.A., Escape from self‐tolerance leads to neonatal insulin‐dependent diabetes mellitus, Autoimmmunity, 30: 199–207, 1999. [DOI] [PubMed] [Google Scholar]
  • 6. Radu D.L., Noben‐Trauth N., Hu‐Li J., Paul W.E., Bona C.A., A targeted mutation in the IL‐4Ra gene protects mice against autoimmune diabetes, Proc. Natl. Acad. Sci. USA, 97: 12700–12704, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Nanda K., Mishra U., Mishra B., A study on osmotic resistance of RBC and ESR in stored blood, J. Indian. Med. Assoc., 96: 205–206, 1998. [PubMed] [Google Scholar]
  • 8. Kowluru R.A., Kern T.S., Engerman R.L., Armstrong D., Abnormalities of retinal metabolism in diabetes or experimental galactosemia. III. Effects of antioxidants, Diabetes, 45: 1233–1237, 1996. [DOI] [PubMed] [Google Scholar]
  • 9. Jain S.H., Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells, J. Biol. Chem., 264: 21340–21345, 1989. [PubMed] [Google Scholar]
  • 10. Popov D, Costache G, Georgescu A, Enache M., Beneficial effects of L‐arginine supplementation in experimental hyperlipemia‐hyperglycemia in the hamster, Cell Tissue Res., 308: 109–120, 2002. [DOI] [PubMed] [Google Scholar]
  • 11. Moffatt J.D., Cocks T.M., Endothelium‐dependent and ‐independent responses to protease‐activated receptor‐2 (PAR‐2) activation in mouse isolated renal arteries, Br. J. Pharmacol., 125: 591–594, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Caps M.T., Perissinotto C., Zierler R.E., Polissar N.L., Bergelin R.O., Tullis M.J., Cantwell‐Gab. K., Prospective study of atherosclerotic disease progression in the renal artery, Circulation, 98: 2866–2872, 1998. [DOI] [PubMed] [Google Scholar]
  • 13. Bauersachs J, Braun C, Franccarolo D., Improvement of renal dysfunction in rats with chronic heart failure after myocardial infarction by treatment with endothelin A receptor antagonist LU 135252, J. Hypertens., 18: 1807–1814, 2000. [DOI] [PubMed] [Google Scholar]
  • 14. Kaplan N.M., Palmer B.F., Impaired renal autoregulation: Implications for the genesis of hypertension and hypertension‐induced renal injury, South Western Internal Medicine Conference, 321: 388–400, 2001. [DOI] [PubMed] [Google Scholar]
  • 15. Sun C.W., Alonso‐Galicia M., Taheri M.R., Flack J.R., Harder D.R., Roman R.J., Nitric oxide‐20‐hydroxyeicosatetraenoic acid interaction in the regulation of K+ channel activity and vascular tone in renal arterioles, Circ. Res., 83: 1069–1079, 1998. [DOI] [PubMed] [Google Scholar]
  • 16. Georgescu A., Popov D., Simionescu M., Mechanisms of impeded bradykinin‐induced vasodilation in experimental hyperlipemia‐hyperglycemia: contribution of nitric oxide and Ca2+ activated K+ channels, in Fund. Clin. Pharmacol., 15: 335–342, 2001. [DOI] [PubMed] [Google Scholar]
  • 17. Torffvit O., Edvinsson L., Relaxing effect of insulin in renal arteries from diabetic rats, Regulatory Peptides, 79: 147–152, 1999. [DOI] [PubMed] [Google Scholar]
  • 18. Popov D., Radu D. L., The role of hyperglycemia in the development of diabetic complications investigated in transgenic mouse model in “Vascular involvement in diabetes: Clinical, experimental and beyond” (Cheta D.M. editor), The Publishing House of the Romanian Academy, 2004. (in press). [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES