Targeted disruption of the Reg protein receptor gene : The relationship of the Reg-Reg receptor system with pancreatic 13-cell replication.
| Project/Area Number |
18590255
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Iwate Medical University (2007)
Tohoku University (2006) |
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Principal Investigator |
NATA Koji Iwate Medical University, School of pharmacy, Professor (90202233)
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| Co-Investigator(Kenkyū-buntansha) |
TAKASAWA Shin Nara Medical University, School of Medicine, Professor (50187944)
NOGUCHI Naoya Tohoku University, Graduate School of Medicine, Assistant Professor (20333792)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | reeenerative medicine / diabetes mellitus / knockout mouse / pancreatic β-cell / the Reg gene family / Reg receptor / Reg受容体 |
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| Research Abstract |
Reg (Regenerating gene) gene encodes a secretory protein that induces pancreatic 13-cell proliferation as an autocrine/paracrine growth factor via Reg receptor (RegR). Accumulating in vitro and in vivo evidence- including that using Reg transgenic and Reg^</-> mice suggest that Reg protein is also involved in regenerative cell proliferation in a variety of tissues such as gastrointestinal, neural and cardiovascular cells. Here, we produced mice with a targeted disruption of RegR to investigate the impact of the Reg-Reg receptor system in tissue regeneration and development. The heterozygous mutant mice (RegR^<+/-> had normal fertility and lifespans and maintained similar body weight and blood glucose level to those of their wild-type cohorts. In addition, there was no difference in pancreatic β-cell mass between RegR^<+/-> mice and the wild type whereas the mRNA and protein levels of RegR in the tissues of RegR^<+/-> mice were about half of the wild type. We then intercrossed RegR^<+/-> mice and found the total absence of RegR^(+/-) pups, indicating that this genotype is embryonic lethal. Timed pregnancies of heterozygotes revealed that RegR^(+/-) die between 8.5 and 9.5 days post coitum. As Reg^(+/-) mice showed the decreased β-cell regenerating activity, we induced pancreatic β-cell replication by partial pancreatectomy in RegR^<+/-> mice. Both the BrdU incorporation and the PCNA positive cells in pancreatic β-cells of RegR^(+/-) mice were decreased compared to those of RegR^(+/+) mice after surgery. These results indicate that the Reg-Reg receptor system is essential for normal mouse development as well as for replication of pancreatic β-cells.
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Report
(3 results)
Research Products
(130 results)
