Establishment and Characterization of the Komeda Diabetes-prone Rat as a Segregating Inbred Strain

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概要

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• The Komeda diabetes-prone (KDP) rat is a spontaneous animal model of human autoimmune type 1 diabetes. By positional cloning of the non-MHC major susceptibility locus Iddm/kdp1, we recently identified a nonsense mutation in Cblb and also found that lymphocytes of KDP rats infiltrate into various tissues, indicating autoimmunity. The maintenance and production of KDP rats has been a critical problem owing to the poor reproductive ability of diabetic animals. To solve the problem, we here established the KDP rat as a segregating inbred strain. We first identified animals that were heterozygous at the Iddm/kdp1 region in a breeding colony of KDP rats. The heterozygous region spans at least from D11Yok1 to Cblb on rat chromosome 11. By mating between the heterozygous rats, we obtained homozygotes, heterozygotes and wild-types with the expected ratio of 1 : 2 : 1 and found that only the homozygotes developed diabetes, suggesting that these genotypes represent those of Iddm/kdp1. We then tried to maintain KDP rats by mating between the heterozygotes, which resulted in a segregating inbred strain. Within 210 d of age, about 80% of Iddm/kdp1 homozygotes developed diabetes with severe insulitis, while neither heterozygotes nor wild-types developed diabetes. The phenotypic characteristics of the homozygotes are the same as those of progeny of diabetic parents in the original KDP rats. The segregating inbred KDP rat strain described here would serve as a useful animal model for autoimmune diseases, including type 1 diabetes.

• 社団法人　日本実験動物学会の論文
• 2003-07-01

著者

• SEINO Susumu

  Department of Molecular Medicine, Chiba University Graduate School of Medicine

• Wang He-yao

  Department Of Cellular And Molecular Medicine Graduate School Of Medicine Chiba University

• Komeda Kajuro

  Division Of Laboratory Animal Science Animal Research Center Tokyo Medical University

• Seino Susumu

  Department Of Cellular And Molecular Medicine Graduate School Of Medicine Chiba University

• Yokoi Norihide

  Department Of Cellular And Molecular Medicine Graduate School Of Medicine Chiba University

• NAMAE Misako

  Division of Laboratory Animal Science Animal Research Center, Tokyo Medical University

• FUSE Masanori

  Division of Laboratory Animal Science Animal Research Center, Tokyo Medical University

• HIRATA Toshiko

  Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University

• Namae Misako

  Division Of Laboratory Animal Science Animal Research Center Tokyo Medical University

• Fuse Masanori

  Division Of Laboratory Animal Science Animal Research Center Tokyo Medical University

• Hirata Toshiko

  Department Of Cellular And Molecular Medicine Graduate School Of Medicine Chiba University

関連論文

• Characterization of Genes Encoding the Pancreatic β-cell ATP-sensitive K^+ Channel in Persistent Hyperinsulinemic Hypoglycemia of Infancy in Japanese Patients
• Sarcolemmal ATP-sensitive K^+ channels and cardiovascular function
• Establishment of Two Substrains, Diabetes-Prone and Non-Diabetic, from Long-Evans Tokushima Lean (LETL) Rats
• Establishment and Characterization of the Komeda Diabetes-prone Rat as a Segregating Inbred Strain
• DISTRIBUTION OF ATP-SENSITIVE K^+ CHANNELS IN PANCREAS
• Morphological Changes in Pancreatic Islets of KATP Channel-Deficient Mice : The Involvement of KATP Channels in the Survival of Insulin Cells and the Maintenance of Islet Architecture
• ATP-Sensitive Potassium Channels : Structures, Functions, and Pathophysiology
• Construction of a prediction model for type 2 diabetes mellitus in the Japanese population based on 11 genes with strong evidence of the association
• Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits

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