| Project/Area Number |
09044335
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Experimental pathology
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| Research Institution | TOKAI UNIVERSITY |
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Principal Investigator |
WATANABE Keiichi TOKAI UNIVERSITY,SCHOOL OF MEDICINE,PROFESSOR, 医学部, 教授 (00055865)
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| Co-Investigator(Kenkyū-buntansha) |
NARISAWA Sonoko THE BURNHAM INSTITUTE (FORMER LA JOLLA CANCER RESERCH FOUNDATION), POSTDOCTRAL F, Postdoctra
MILLAN Jose Luis THE BURNHAM INSTITUTE (FORMER LA JOLLA CANCER RESEARCH FOUNDATION), PROFESSOR, Senior Sta
TAKEKOSHI Susumu TOKAI UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT RESEARCHER, 医学部, 助手 (70216878)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | ALKALINE PHOSPHATASE (AP) / EMBRYONAL AP / TISSUE NONSPECIFIC AP / KOCK-OUT MICE / alkaline phophatase(AP) |
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| Research Abstract |
There are 3 to 4, depending on the difference of the animal species, isozymes of alkaline phosphatase (AP), and they are widely distributed in those animal bodies. However, little is known about their exact biological functions and left as a "mysterious enzyme". Attempts were thus made to disclose those biological functions and significances by establishing "knock-out mice" for the genes of mouse APs ((1)D embryonic (EAP), (2) tissue non-specific (TNAP) and (3) intestinal (IAP)) and by further investigations on genomic and phenotypic expression of those genes and diverse patho-physiological phenomena which may appear in those animals. Since the establishment of "IAP knock-out mice" is still in process and "EAP knock-out mice" did not show any significant phenotypic changes, the observations were centered to the changes appeared in the "TNAP knock-out mice" . (1) The majority of these "knock-out mice" died during the weaning period (averagely 2 weeks) after they exhibited characteristic epileptic seizure. Sine it is a well documented fact that pyridoxal (vitaminB^6=VB^6) deficient mice fell in the very similar epileptic seizure, we presume TNAP gene inactivation would cause in VB^6 depletion which is not experimentally proved yet. TNAP could be taking an important role in dephosphorylation of pyridoxal phosphates. (2) Another conspicuous pathological change observed in those "knock-out mice" was abnormal mineralization appeared in bones of almost whole bodies. The deficiency of TNAP in osteoblasts which show marked structural deformity may strongly be responsible for thatpathology. Concerning IAP knockout mouse preparation, ES cells transfected with the targeting vector described before. One of the clones was confirmed as a homologous recombinant by Southern blots, and this clone was injected into the bastocysts. We are currently breeding the four chimeric males in order to obtain germline heterozygote mice.
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