1995 Fiscal Year Final Research Report Summary
ESTABLISHMENT OF MICE DEFICTENT IN A VASOACTIVE PEPTIDE BY GENE TARGETING AND THEIR APPLICATION TO PATHOPHYSIOLOGICAL ANALYSIS
| Project/Area Number |
06454286
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | University of Tokyo |
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Principal Investigator |
KURIHARA Hiroki University of Tokyo, Faculty of Medicine, ASSISTANT, 医学部(病), 助手 (20221947)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Tatsuhiko University of Tokyo, Faculty of Medicine, ASSISTANT, 医学部(病), 助手 (90170266)
NAGAI Ryozoh University of Gunma, Faculty of Medicine, PROFESSOR, 医学部, 教授 (60207975)
ISHIKAWA Takatoshi University of Tokyo, Faculty of Medicine, PROFESSOR, 医学部(医), 教授 (30085633)
KUMADA Mamoru University of Tokyo, Faculty of Medicine, PROFESSOR, 医学部(医), 教授 (00110487)
YAZAKI Yoshio University of Tokyo, Faculty of Medicine, PROFESSOR, 医学部(病), 教授 (20101090)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Endothelin-1 / Gene-targeting / Knock-out mice / Congenital diseases / Blood pressure / Transgenic mice / Neural crest / Development |
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| Research Abstract |
In the present study, we have clarified the novel developmental role and the implication in blood pressure regulation of ET-1 through the establishment of ET-1-knockout mice by gene targeting and their analysis. We hypothesized that ET-1 may serve as a mediator of the epithelial-mesenchymal interaction in the development of neural crest cells which plays an important role in the formation of the pharyngeal arches and cardiovascular system. Particularly, the phenotype of ET-1 knockout homozyotes (craniofacial abnormalities+great vessel malformations+ventricular septal defect) and human congenital diseases such as CATCH22 and velo-cardio-facial syndrome are very similar, suggesting that ET-1 knockout mice may give a clue to clarification of the genetic mechanism of these diseases and development of new therapeutic strategis. In ET-1 knockout heterozygotes, blood pressure was paradoxically elevated, indicating that ET-1 may not simply act as a pressor and the involvement of ET-1 in the regulation of cardiovascular homeostasis is rather complicated. Subsequently, we have found abnormalities in respiration and response to stress in addition to blood pressure elevation in ET-1 knockout mice. These findings have shed a light on the role of ET-1 in central cardiopulmonary regulation. In the elucidation of the pathophysiological role of ET-1, it would be of great use to make disease models inET-1 knockout mice. Establishment of disease models including atherosclerosis and hypertension in ET-1 knockout mice is in progress. Furthermore, we have succeeded in establishing the vessel-selective gene expression system using the ET-1 gene promoter region and ET-1-overexpressing mice using this system. Systematic analysis of both ET-1 knockout mice and ET-1-overexpression mice is expected to further elucidate the pahophysiological role of ET-1.
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Research Products
(20 results)
