| Project/Area Number |
09480247
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Shimane University |
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Principal Investigator |
FUNAKI Kenji Faculty of Education, Shimane University, Associate Professor, 教育学部, 助教授 (90091579)
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| Co-Investigator(Kenkyū-buntansha) |
OSHIMURA Mitsuo Faculty of Medicine, Tottori University, Professor, 教育学部, 教授 (20111619)
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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 |
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | microcell-mediated chromosome transfer / human chromosome 21 / mouse embryonic stem cell / chimeric mouse / キメラマウス / ヒト染色体 / 胚幹細胞 / ES細胞 / マウス / キメラ |
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| Research Abstract |
In present study, hChr.21 was introduced into mouse embryonic stem (ES) cells via microcell-mediated chromosome transfer (MMCT), and viable chimeric mice were produced from them. We analyzed theses mice as followings. Metaphase spreads of various tissues from four chimeric mice were examined by Fluorescence in situ hybridization (FISH) to evaluate the stability of hChr.21 in somatic cells. The percentage of the spreads containing the hChr.21 showed 50-100%. RT-PCR analysis of one of these mice showed that several genes on hChr.21 were expressed in a proper tissue-specific manner. Finally, we have determined that chimeric mice could transmit hChr.21 fragment (hChr.21f) to their offspring through germline. FISH analysis of various tissues in these germline mice showed that the retention of hChr.21f of them were lower than that of chimeric mice.
In anatomical and histological observation of 11 chimeric mice dead in perinatal period, it was found that aplasia of the sternum and remarkable decrease of germ cell occurred in all of them, and various histological abnormality occurred sporadically in heart, liver and kidney. As a control, four chimeric mice induced hChr.2f (containing immunoglobulin genes) were anatomically and histologically studied. In almost of them delayed ossification of the cervical vertebra centrum, aplasia of the sternum and polydactyly of the forelimb were observed, and hypertrophy and histologically various abnormality in hert, liver and kidney occurred sporadically. It is highly possible that remarkable decrease of germ cell in the hChr.21-chimeric mice and polydactyly in the hChr.2f-chimeric mice are related to the gene(s) on the human chromosome introduced.
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