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演題詳細

Poster

神経発達障害
Neurodevelopmental Disorders

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

父親のPax6変異は加齢による仔の音声コミュニケーション障害の影響を早期に生じさせる
Paternal Pax6 mutation accelerates vocal communication deficit in mouse offspring caused by paternal aging

  • P2-355
  • 木村 龍一 / Ryuichi Kimura:1 吉崎 嘉一 / Kaichi Yoshizaki: 小池 浩平 / Kohei Koike: 稲田 仁 / Hitoshi Inada: 大隅 典子 / Noriko Osumi: 
  • 1:東北大学大学院 / Division of Developmental Neuroscience, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine 

In rodent, advanced paternal age induces offspring abnormal behaviors including vocal communication after maternal separation, yet how paternal aging affects their offspring phenotypes is an intriguing issue. Here, we report that paternal Pax6 mutation accelerates the decrease in ultrasonic vocalization (USV) calls caused by advanced paternal age. Spontaneous Pax6 mutant (Sey) sire mice at each stage of young (3-month-old), middle-aged (6-8-month-old), and advanced-aged (>12-month-old) were mated with young (3-month-old) wiled-type (WT) females. Their offspring were separated from the dams at postnatal day 6 and the number of USV calls was measured for 5 minutes separation. Sey offspring derived from middle-aged Sey sire showed significant decrease in the number of USV calls compared to WT littermates. This reduction was not considered to be attributed to Pax6 haploinsufficiency of offspring because the number of USV calls was comparable between Sey offspring and WT litter mates derived from young Sey sires. We found the expression of Pax6 in spermatocytes and it is reported that Pax6 interacts with the BAF complex and has role in chromatin remodeling, which led us to ask whether Pax6 haploinsufficiency accelerates paternal aging-related epigenetic changes in spermatocytes. Quantitative analysis demonstrated an intriguing change in histone methylation in Sey spermatocytes. Because advanced-aged WT spermatocytes also showed a common epigenetical change, it is suggested that paternally inherited Pax6 mutation accelerates vocal communication deficit in offspring caused by paternal aging possibly through the epigenetical change during spermatogenesis. We are currently testing whether the altered histone methylation remains in sperm and in the developing brain.

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