| 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)
田中 彰彦 東京医科大学, 医学部, 助手 (40287149)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥5,800,000 (Direct Cost: ¥5,800,000)
|
|---|
| Keywords | SDT rat / Type 2 diabetes / Hyperglycemia / Linkage analysis / Susceptibility genes / Microsatellite marker / Glucose intolerance / QTL analysis / ラット / 免疫組織 / II型糖尿病 |
|---|
| 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.
|
