Genetic Analysis of Diabetes in a Spontaneously Diabetic Non-obese Torii Rat, a Newly Established Animal Model

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 10480236
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Tokyo Medical University
• Principal Investigator: KOMEDA Kajuro Tokyo Medical University, Medicine, Associate Professor, 医学部, 助教授 (90074533)
• Co-Investigator(Kenkyū-buntansha): KANAZAWA Yasunori Jichi Medical School, Medicine, Professor, 医学部, 教授 (10010399) ; KANAZAWA Maaso Tokyo Medical University, Medicinem Lecture, 医学部, 講師 (10147184)
• Project Period (FY): 1998 – 2000
• Keywords: SDT rat / Type 2 diabetes / Hyperglycemia / Linkage analysis / Susceptibility genes / Microsatellite marker / Glucose intolerance / QTL analysis

Research Abstract

A spontaneously diabetic Torii (SDT) rat is an animal model for type 2 diabetes with non-obese in humans. A cumulative incidence of diabetes of 100% was noted by 30weeks of age in male rats, while it was only 33.3% even by 65 weeks of age in the female rats (Int.J Exp Diab Res, 1 : 89-100, 2000). We performed pathological and physiological characterizations and QTL analysis using a backcross panel {(BN x SDT) F1 x SDT}. All of the F1 progenies showed no sign of glucose intolerance at 20 weeks of age and hyperglycemia at 25 weeks of age. Only 27 rats (8.5%) out of 319 male backcrosses showed glucose intolerance at 20 weeks of age or hyperglcemia at 25 weeks of age. By the first genome-wide scan for responsible genes in this strain using SSLP markers, we mapped five QTLs for glucose intolerance ; these were Niddm/sdt 1, Niddm/sdt2, Niddm/sdt3, Niddm/sdt4, and Niddm/sdt5 on chromosomes 1, 2, 11, 18 and X, respectively. They were mapped on chromosomal regions that were not homologous to human diabetes-susceptibility loci already reported. For these QTLs, prevalence of SDT alleles significantly exacerbated glucose intolerance. Furthermore, a synergistic interaction among these QTLs contributed to the onset of glucose intolerance. These genetic loci are responsible for glucose intolerance in the SDT rat.

Research Products

• [Publications] Masuyama, T., Ishibiki, J., Awata, T., Noda, M., Kanazawa, Y., Sugawara, M., Komeda, K.: "An improved genetic linkage map of rat chromosome 20"Comparative Medicine. 50. 345-349 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shinohara, M., Masuyama, T., Shoda, T., Takahashi, T., Katsuda, Y., Komeda, K., Kuroki, M., Kakehashi, A., Kanazawa, Y.: "A new spontaneously diabetic non-obese Torii rat strain with severe ocular complications"Int.J.Experimental Diabetes Research. 1. 89-100 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Masuyama, T., Ishikiki, J., Awata T.0 Noda, M., Kanazawa Y., Sugawara, M., and Komeda, K: "An improved genetic linkage map of rat chromosome 20."Comparative Med. 50. 345-349 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shinohara, M., Masuyama, T., Shoda T., Takahashi, T., Katsuda, Y., Komeda, K., Kuroki, M., Kakehashi, A., and Kanazawa, Y.: "A new spontaneously diabetic non-obese Torii rat strain with severe ocular complications."Int'l Jnl. Exp. Diab. Res. 1. 89-100 (2000)
  • Description: 「研究成果報告書概要(欧文)」より