Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA

T. Yamaoka, C. Nishimura, K. Yamashita, M. Itakura, T. Yamada, J. Fujimoto, Y. Kokai

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

To investigate the role of human aldose reductase (hAR) in the pathogenesis of diabetic complications, we generated transgenic mice carrying hAR cDNA driven by the murine MHC class I molecule promoter (hAR-Tg). Northern and Western blot analyses and immunoassay of hAR revealed that both hAR mRNA and the protein were expressed in all tissues tested. Thrombosis in renal vessels and fibrinous deposits in Bowman's capsule were observed in 6-week-old hAR-Tg mice fed a normal diet. Ingestion of a 30% glucose diet for 5 days caused sorbitol concentrations in the liver, kidney, and muscle of hAR-Tg mice to be elevated significantly. Seven-week-old hAR-Tg mice fed a 20% galactose diet for 7 days developed cataracts and occlusion of the retinochoroidal vessels, in addition to pathological changes in the kidney. Despite an elevated aldose reductase level in hAR-Tg mice and their intake of an aldose diet, no histopathological changes were found in other tissues, including the brain, lungs, heart, thymus, spleen, intestine, liver, muscle, spinal cord, or sciatic nerve. Results suggest that target organs of diabetic complications, such as the kidney, lens, and retina are sensitive to damage associated with a high level of AR expression, but other organs are not; the susceptibility of each organ to diabetic complications is determined by not only hAR but also other factors.

Original languageEnglish
Pages (from-to)255-261
Number of pages7
JournalDiabetologia
Volume38
Issue number3
DOIs
Publication statusPublished - 1995 Mar

Fingerprint

Aldehyde Reductase
Transgenic Mice
Complementary DNA
Diabetes Complications
Diet
Kidney
Bowman Capsule
Muscles
Spinal Nerves
Sorbitol
Liver
Sciatic Nerve
Galactose
Immunoassay
Northern Blotting
Cataract
Thymus Gland
Lenses
Intestines
Retina

Keywords

  • aldose reductase
  • diabetic angiopathies
  • diabetic nephropathies
  • diabetic retinopathy
  • Transgenic mice

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Yamaoka, T., Nishimura, C., Yamashita, K., Itakura, M., Yamada, T., Fujimoto, J., & Kokai, Y. (1995). Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA. Diabetologia, 38(3), 255-261. https://doi.org/10.1007/BF00400627

Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA. / Yamaoka, T.; Nishimura, C.; Yamashita, K.; Itakura, M.; Yamada, T.; Fujimoto, J.; Kokai, Y.

In: Diabetologia, Vol. 38, No. 3, 03.1995, p. 255-261.

Research output: Contribution to journalArticle

Yamaoka, T, Nishimura, C, Yamashita, K, Itakura, M, Yamada, T, Fujimoto, J & Kokai, Y 1995, 'Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA', Diabetologia, vol. 38, no. 3, pp. 255-261. https://doi.org/10.1007/BF00400627
Yamaoka T, Nishimura C, Yamashita K, Itakura M, Yamada T, Fujimoto J et al. Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA. Diabetologia. 1995 Mar;38(3):255-261. https://doi.org/10.1007/BF00400627
Yamaoka, T. ; Nishimura, C. ; Yamashita, K. ; Itakura, M. ; Yamada, T. ; Fujimoto, J. ; Kokai, Y. / Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA. In: Diabetologia. 1995 ; Vol. 38, No. 3. pp. 255-261.
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