Journal
CELL REPORTS
Volume 19, Issue 2, Pages 335-350Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.03.052
Keywords
-
Categories
Funding
- Swanson Biotechnology Center
- National Science Foundation Graduate Research Fellowship [1122374, 2013169249]
- ETH Zurich
- NCCR-MSE
- Simons Center for the Social Brain at MIT postdoctoral fellowship
- NIMH [F31-MH111157]
- HHMI [NS046789]
- SFARI/Simons Foundation [306063, 6927482]
- McGovern Internal Funding Poitras Gift [1631119]
- Stanley Center
- Nancy Lurie Marks Family Foundation [6928117]
- NIH through NIMH [5DP1-MH100706, 1R01-MH110049]
- NSF
- New York Stem Cell Foundation
- Howard Hughes Medical Institute
- Simons Foundation
- Paul G. Allen Family Foundation
- Vallee Foundation
- Skoltech-MIT Next Generation Program
Ask authors/readers for more resources
Autism spectrum disorder (ASD) is a heterogeneous disease, but genetically defined models can provide an entry point to studying the molecular underpinnings of this disorder. We generated germline mutant mice with loss-of-function mutations in Chd8, a de novo mutation strongly associated with ASD, and demonstrate that these mice display hallmark ASD behaviors, macrocephaly, and craniofacial abnormalities similar to patient phenotypes. Chd8(+/)mice display a broad, brain-region-specific dysregulation of major regulatory and cellular processes, most notably histone and chromatin modification, mRNA and protein processing, Wnt signaling, and cell-cycle regulation. We also find altered synaptic physiology in medium spiny neurons of the nucleus accumbens. Perturbation of Chd8 in adult mice recapitulates improved acquired motor learning behavior found in Chd8(+/)-animals, suggesting a role for CHD8 in adult striatal circuits. These results support a mechanism linking chromatin modification to striatal dysfunction and the molecular pathology of ASD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available