2006 Fiscal Year Final Research Report Summary
Searches for the molecular pathogenesis of skeretal and neuronal system from serum calcium-decreasing factor, caldecrin, knock out mouse
| Project/Area Number |
16591864
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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 |
Functional basic dentistry
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| Research Institution | Meikai University |
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Principal Investigator |
TOMOMURA Akito Meikai University, Biochemstry, Professor, 歯学部, 教授 (60188810)
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| Co-Investigator(Kenkyū-buntansha) |
INABA Akemi Meikai University, Biochemstry, Asistant Professor, 歯学部, 助教 (50151585)
FUJIMOTO Kengo Meikai University, Biochemstry, Asistant Professor, 歯学部, 助教 (90286013)
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| Project Period (FY) |
2004 – 2006
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| Keywords | calcium / bone resorption / alzheimer / protease |
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| Research Abstract |
Caldecrin is a serum calcium-decreasing factor which was purified and cloned from pancreas, and seems to be a hypocalcemic factor with acute pancreatitis. It belongs to the elastase family, but its calcium-decreasing activity did not clear connect with protease activity. We identified that the calcium-decreasing activity of caldecrin suppressed osteoclastic bone resorption and osteoclast formation from bone marrow. We also identified that caldecrin suppressed Ca ion-calcineurin system in the signal transduction pathway of the RANKL-induced osteoclstic formation. On the other hand, caldecrin expresses in the brain, and its physiological function is not clear. We examined whether caldecrin suppressed an amyloid formation in the senile plaque of Alzheimer's disease. Caldecrin digested amyloid β peptides 40 and 42 with time-dependent manner, and also suppressed amyloid formation of amyloid, β peptide 42. In addition, neurotoxicity of these digested peptide fragments was disappeared. These results suggest that caldecrin expressed in the brain digests amyloid β and suppresses amyloid formation by protease activity. Therefore we made caldecrin gene destruction mouse for the search of physiological and pathological functions in the bone and nervous system. A targeting vector for caldecrin gene was recombinated into an C57BL/6 embryonic stem cell and selected G418-resistant clones. We obtained several clones analyzed by PCA and southern blot hybridization.
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