Identification of the responsible genes for a novel mouse model of spondylothoracic dysostosis
| Project/Area Number |
17K11960
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthodontics/Pediatric dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
FUJIKAWA JUNJI 大阪大学, 歯学部附属病院, 医員 (40760377)
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| Co-Investigator(Kenkyū-buntansha) |
秋山 茂久 大阪大学, 歯学部附属病院, 准教授 (00283797)
村上 旬平 大阪大学, 歯学部附属病院, 講師 (70362689)
三浦 郁生 国立研究開発法人理化学研究所, バイオリソース研究センター, 開発技師 (70624948)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 骨系統疾患 / 自然発症 / 解剖学 |
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| Outline of Final Research Achievements |
A strain (FR mouse) that closely resembles the phenotype of spondylothoracic dysostosis, which is a skeletal dysplasias, was found in wild type mouse colonies. We started the study aiming to elucidate the cause of spondylothoracic dysostosis and the normal skeleton formation mechanism. First, we narrowed down multiple candidate genes such as Dnajc19 and Lrrc31 by Exome sequencing and Sanger sequencing. However, another approach was required because the phenotype of these knockout mice was different from that of FR mice, such as weight loss, and there was no mutation that correlated with all FR mice. Therefore, SNP analysis was performed on a total of 74 fetuses (13 pregnant mice) of FR mouse fetuses and wild-type mouse fetuses of the same litter. These analyzes suggested that the responsible gene of FR mouse may be located downstream of chromosome 8.
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| Academic Significance and Societal Importance of the Research Achievements |
脊椎胸郭異骨症は頸椎と肋骨の異常を特徴とする骨系統疾患であり、脊椎・肋骨の癒合、短縮した脊椎等が認められる。このため肺の発達が阻害され呼吸不全のリスクが高い。原因遺伝子は複数明らかになってはいるが治療法の確立に至っていない。以前より脊椎胸郭異骨症の表現型と酷似する系統を野生型マウスコロニーから認めており、新たな原因遺伝子の解明を目指しこのマウス系統の解析を行なったところ、8番染色体の下流にある可能性が示唆された。新たな原因遺伝子の同定までは至らなかったが、存在の可能性は高まった。乳児期までの死亡率が約50％とも言われるこの疾患の治療法確立の一助となるべく研究の継続が必要である。
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Report
(4 results)
Research Products
(6 results)
