Identification of Genetic Mutation in Papillon Dog Neuroaxonal Dystrophy, and Application as a Novel Animal Model for Human Infantile Neuroaxonal Dystrophy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26870118
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Veterinary medical science
• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• 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

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.

Free Research Field

獣医学