Summary: A new study examines the role paternal aging may play in the development of neurodevelopmental disorders in offspring with an inherited genetic mutation of Pax6.
Source: Tohoku University.
Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD) are on the rise but its underlying mechanisms are poorly understood.
Noriko Osumi, Kaichi Yoshizaki and colleagues at Tohoku University’s Graduate School of Medicine collaborated with Shigeru Wakana and Tamio Furuse at RIKEN Bio-Resource Center, and Tucci Valter at Istituto Italiano di Tecnologia, to conduct comprehensive behavioral analyses on how paternal aging influences the behavior of offspring that inherit a genetic risk (a mutation in Pax6 gene).
In the experiments, in order to minimize the physical influence of the father, the male mouse was isolated and in vitro fertilization was used to impregnate the female. The researchers found that the offspring of young fathers exhibited impaired vocal communication, while the offspring of older fathers exhibited hyperlocomotion.
The results are significant for both animal researchers and the public. For researchers working on animal models, it shows that the age of male mice can influence the behavior of the offspring, so this should be a consideration when they are used to mate.
For the public, the research shows that paternal aging may exacerbate genetic risks – this could explain why there is a rapid rise in the ratio of children with ASD or ADHD, due to men having children later in life.
Pax6 gene encodes a transcription factor that regulates expression of many downstream genes and is known to be related to ASD.
Funding: The research was supported in part by KAKENHI (25640002 to K.Y. and 16H06530 to N.O.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Source: Noriko Osumi – Tohoku University
Image Source: NeuroscienceNews.com image is credited to Tohoku University Graduate School of Medicine.
Original Research: Full open access research for “Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders” by Kaichi Yoshizaki, Tamio Furuse, Ryuichi Kimura, Valter Tucci, Hideki Kaneda, Shigeharu Wakana, and Noriko Osumi in PLOS ONE. Published online November 17 2016 doi:10.1371/journal.pone.0166665
[cbtabs][cbtab title=”MLA”]Tohoku University “Link Between Paternal Aging, Autism and ADHD.” NeuroscienceNews. NeuroscienceNews, 9 December 2016.
<https://neurosciencenews.com/neurodevelopment-paternal-age-5716/>.[/cbtab][cbtab title=”APA”]Tohoku University (2016, December 9). Link Between Paternal Aging, Autism and ADHD. NeuroscienceNew. Retrieved December 9, 2016 from https://neurosciencenews.com/neurodevelopment-paternal-age-5716/[/cbtab][cbtab title=”Chicago”]Tohoku University “Link Between Paternal Aging, Autism and ADHD.” https://neurosciencenews.com/neurodevelopment-paternal-age-5716/ (accessed December 9, 2016).[/cbtab][/cbtabs]
Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders
Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD) have increased over the last few decades. These neurodevelopmental disorders are characterized by a complex etiology, which involves multiple genes and gene-environmental interactions. Various genes that control specific properties of neural development exert pivotal roles in the occurrence and severity of phenotypes associated with neurodevelopmental disorders. Moreover, paternal aging has been reported as one of the factors that contribute to the risk of ASD and ADHD. Here we report, for the first time, that paternal aging has profound effects on the onset of behavioral abnormalities in mice carrying a mutation of Pax6, a gene with neurodevelopmental regulatory functions. We adopted an in vitro fertilization approach to restrict the influence of additional factors. Comprehensive behavioral analyses were performed in Sey/+ mice (i.e., Pax6 mutant heterozygotes) born from in vitro fertilization of sperm taken from young or aged Sey/+ fathers. No body weight changes were found in the four groups, i.e., Sey/+ and wild type (WT) mice born to young or aged father. However, we found important differences in maternal separation-induced ultrasonic vocalizations of Sey/+ mice born from young father and in the level of hyperactivity of Sey/+ mice born from aged fathers in the open-field test, respectively, compared to WT littermates. Phenotypes of anxiety were observed in both genotypes born from aged fathers compared with those born from young fathers. No significant difference was found in social behavior and sensorimotor gating among the four groups. These results indicate that mice with a single genetic risk factor can develop different phenotypes depending on the paternal age. Our study advocates for serious considerations on the role of paternal aging in breeding strategies for animal studies.
“Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders” by Kaichi Yoshizaki, Tamio Furuse, Ryuichi Kimura, Valter Tucci, Hideki Kaneda, Shigeharu Wakana, and Noriko Osumi in PLOS ONE. Published online November 17 2016 doi:10.1371/journal.pone.0166665