Identification of Genetic Mutation in Papillon Dog Neuroaxonal Dystrophy, and Application as a Novel Animal Model for Human Infantile Neuroaxonal Dystrophy
Project/Area Number |
26870118
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
Veterinary medical science
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Research Institution | The University of Tokyo |
Principal Investigator |
Tsuboi Masaya 東京大学, 大学院農学生命科学研究科(農学部), 特任助教 (20721963)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | イヌゲノム / 神経軸索ジストロフィー / 神経疾患 / 遺伝子病 / パピヨン / オートファジー / 遺伝病 |
Outline of Final Research Achievements |
The aim of this research is to clarify the molecular pathogenesis of neuroaxonal dystrophy (NAD) in Papillon dogs. First, we carried out whole exome sequencing analysis against three NAD cases and five unaffected control Papillon dogs, and identified 10 candidate mutations. Among them, three candidates were determined to be “deleterious” by in silico pathogenesis evaluation, and only the PLA2G6 c.1579G>A mutation had an association with the presence or absence of the disease, suggesting that it may be a causal mutation of canine NAD. Although we performed massive screening mutation analysis, we could not expose any mutation-carrier dog, as the mutation penetrance was assumed to be extremely low. Further histopathological research revealed accumulation of autophagy-related proteins in the lesion, indicating aberrance in autophagy mechanism.
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Report
(4 results)
Research Products
(3 results)
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[Journal Article] Identification of the PLA2G6 c.1579G>A missense mutation in Papillon dog neuroaxonal dystrophy using whole exome sequencing analysis.2017
Author(s)
Tsuboi M, Watanabe M, Nibe K, Yoshimi N, Kato A, Sakaguchi M, Yamato O, Tanaka M, Kuwamura M, Kushida K, Ishikura T, Harada T, Chambers JK, Sugano S, Uchida K, Nakayama H.
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Journal Title
PLoS One
Volume: 12
Issue: 1
Pages: 1-17
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Whole Exome Sequence法によるイヌ遺伝性神経疾患の原因遺伝子同定2015
Author(s)
坪井誠也, 渡邊学, 二瓶和美, 吉見奈津子, 加藤明久, 阪口雅弘, 大和修,櫛田和哉,チェンバーズジェームズ, 菅野純夫, 内田和幸, 中山裕之
Organizer
第11回獣医内科学アカデミー学術大会
Place of Presentation
パシフィコ横浜
Year and Date
2015-02-20 – 2015-02-22
Related Report
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