2017 Fiscal Year Final Research Report
The functional role of BRAF in cardiac development and bone formation
| Project/Area Number |
15K19598
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | CFC症候群 / RASopathies / RAS/MAPKシグナル伝達経路 / BRAF / 先天性心疾患 / 疾患モデルマウス / 遺伝性疾患 |
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| Outline of Final Research Achievements |
Germline mutations in BRAF have been identified in 70% of patients with cardio-facio-cutaneous (CFC) syndrome, which is characterized by heart defects, distinctive facial features, short stature and ectodermal abnormalities. We recently demonstrated that mice expressing a Braf Q241R mutation on a C57BL/6J background are embryonic/neonatal lethal, with multiple congenital defects, preventing us from analyzing the phenotypic consequences after birth. Here, to further explore the pathogenesis of CFC syndrome, we backcrossed these mice onto an ICR genetic background. The BrafQ241R/+ ICR mice exhibited growth retardation, sparse and ruffled fur, a hunched appearance, craniofacial dysmorphism and heart defects, including pulmonary stenosis and atrial septal defects. These data suggest that the heterozygous BrafQ241R/+ ICR mice show similar phenotypes as CFC syndrome after birth and will be useful for elucidating the pathogenesis and potential therapeutic strategies for CFC syndrome.
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| Free Research Field |
遺伝学
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