| Project/Area Number |
04557122
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Department of Pharmacology and Toxicology, Kyorin University School of Medicine (1993-1994)
The University of Tokyo (1992) |
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Principal Investigator |
ENDOU Hitoshi Kyorin University School of Medicine, Department of Pharmacology and Toxicology Professor, 医学部, 教授 (20101115)
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| Co-Investigator(Kenkyū-buntansha) |
OBINATA Masuo Tohoku University, Institute of Development, Aging and Cancer Professor, 加齢医学研究所, 教授 (10099971)
SEKINE Takashi Kyorin University School of Medicine, Department of Pharmacology and Toxicology, 医学部, 助手 (50255402)
MIZUNO Akiko Kyorin University School of Medicine, Department of Pharmacology and Toxicology, 医学部, 助手 (60255403)
TAKEDA Michio Kyorin University School of Medicine, Department of Pharmacology and Toxicology, 医学部, 助手 (40255401)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥17,400,000 (Direct Cost: ¥17,400,000)
Fiscal Year 1994: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1993: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1992: ¥9,900,000 (Direct Cost: ¥9,900,000)
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| Keywords | transgenic mouse / SV40 large T antigen gene / single nephron / immortalized cell lines / nephron segment-specific enzyme / nephron segment-specific metabolism / ATP receptor / cisplatin / トランスジエニックマウス / 温度感受性因子 / 近位尿細管 / 集合尿細管 / サイクリツクAMP / アルカリフォスファターゼ / SV40-T抗原 / サイクリックAMP / アンモニア産生 |
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| Research Abstract |
The results that we could obtain according to our plan are as follows.
1)Establishment of immortalized cultured cell lines from transgenic mouse kidneys.
A ts-SV40 large T-antigen gene was injected into pronuclei of fertilized eggs of C57BL/6 mice, and mice of first generation were abtained. Various nephron segments were microdissected from collagenase-treated kidneys and cultivated. Cells thus made can be maintained over 100 passages.
2)Characterization of established cell lines.
Several characters like nephron segment-specific enzymes, metabolisms, and hormone recepters in the cell lines were compared with those in freshly isolated respective nephron segments. These cell lines maintained most site-specific characters except gamma-GTP activity, gluconeogenesis and porathyroid hormone receptor.
3)Application of these cell lines for pharmacological and toxicological studies.
Cells originated from the terminal proximal tubule could be successfully applied for the evaluation of cisplatin-induced nephrotoxicity. Since ATP-purinoceptor was highly expressed in cells form outer medullary collecting duct, these cells might be suitable sample for cloning cDNA of ATP receptr protein (s) . This trial is now under investigation.
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