Elucidation of etiology and phenotypic control in a porcine autosomal dominant genetic disease model
| Project/Area Number |
15H02480
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Integrative animal science
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| Research Institution | Meiji University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大鐘 潤 明治大学, 農学部, 専任准教授 (50313078)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥41,730,000 (Direct Cost: ¥32,100,000、Indirect Cost: ¥9,630,000)
Fiscal Year 2018: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2017: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2016: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2015: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
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| Keywords | ブタ / 遺伝子改変動物 / 常染色体優性遺伝病 / ハプロ不全 / マルファン症候群モデル / エピジェネティクス / CpG shore / メチル化修飾 / 発生工学 / 遺伝学 / 応用動物 / ゲノム |
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| Outline of Final Research Achievements |
Marfan syndrome (MFS) is an autosomal dominant genetic disease. We established a porcine model for MFS by introducing a mutation (Glu433AsnfsX98) in the Fibrillin1 (FBN1) gene. We also identified a single nucleotide polymorphism (SNP) in FBN1 promotor CpG shore in a pig. Using the offspring (F1) obtained by mating of MFS females and a SNP-identified male, relationship between the methylation status of FBN1 CpG shore and the expression level of FBN1 was identified. Our results suggested that epigenetic modification of the responsible gene expression is involved in the etiology of MFS exhibiting haploinsufficiency.
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| Academic Significance and Societal Importance of the Research Achievements |
常染色体優性遺伝病において、正常アリルのみからの発現量では遺伝子産物量が不足するために発症するものはハプロ不全と呼ばれる。ハプロ不全では原因遺伝子の塩基配列のみからは十分説明できないため、発症の有無に浸透度、発症組織の違いなどに表現度といった遺伝学用語を当てはめて、統計的な確率論として議論してきた。本研究では、ハプロ不全性の優性遺伝病の発症機序にエピジェネティクスからアプローチしている。エピジェネティクス研究によってハプロ不全性優性遺伝病の病態発現の制御が解明できれば、疾患モデルブタを用いた前臨床的研究や創薬研究が飛躍的に発展することが期待できる。
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Report
(5 results)
Research Products
(50 results)
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[Journal Article] Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts2016
Author(s)
Umeyama K, Watanabe K, Watanabe M, Horiuchi K, Nakano K, Kitashiro M, Matsunari H, Kimura T, Arima Y, Sampetrean O, Nagaya M, Saito M, Saya H, Kosaki K, Nagashima H & Matsumoto M
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Journal Title
Sci Rep.
Volume: 6:24413
Issue: 1
Pages: 1-4
DOI
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Peer Reviewed / Open Access
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[Presentation] Phenotype of homozygouse fibrillin-1 (FBN1) mutant pigs2018
Author(s)
Umeyama K., Arai Y., Nakano K., Uchikura A., Watanabe M., Matsunari H., Saito M., Saya H., Matsumoto M., Nagaya M., Ohgane J., Nagashima H
Organizer
10th International Research Symposium on Marfan Syndrome and Related Disorders
Related Report
Int'l Joint Research
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[Presentation] Phenotypic variation in the cloned pigs with heterozygous fibrillin-1 mutation2017
Author(s)
Umeyama K, Arai Y, Nakano K, Fukuda T, Umeki I, Uchikura A, Kasai Y, Matsunari H, Nagaya M, Watanabe M, Ohgane J and Nagashima H
Organizer
4th World Congress of Reproductive Biology
Related Report
Int'l Joint Research
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[Presentation] 変異型fibrillin-1遺伝子を有するブタの上行大動脈の病理解析2016
Author(s)
梅山一大, 新井良和, 中野和明, 内倉鮎子, 渡邊将人, 松成ひとみ, 齋藤正寛, 木村徳宏, 渡邊航太, 堀内圭輔, 北城雅照, 有馬好美, サンペトラオルテア, 小崎健次郎, 佐谷秀行, 松本守雄, 長屋昌樹, 大鐘潤, 長嶋比呂志
Organizer
第57回日本脈管学会総会
Place of Presentation
奈良
Year and Date
2016-10-13
Related Report
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[Presentation] ホモ変異型fibrillin-1遺伝子を有するブタの表現型2016
Author(s)
梅山一大, 新井良和, 中野和明, 内倉鮎子, 渡邊將人, 松成ひとみ, 齋藤正寛, 佐谷秀行, 松本守雄, 長屋昌樹, 大鐘潤, 長嶋比呂志
Organizer
第48回日本結合組織学会学術大会
Place of Presentation
長崎
Year and Date
2016-06-24
Related Report
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