| Autor: |
Moffat JJ; Developmental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.; Department of Neurology, University of California San Francisco, San Francisco, CA, 94153, USA., Jung EM; Department of Molecular Biology, Pusan National University, Busan, 46241, Republic of Korea., Ka M; Research Center for Substance Abuse Pharmacology, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea., Jeon BT; Department of Biological Sciences, Kent State University, Kent, OH, 44242, USA., Lee H; Department of Biological Sciences, Kent State University, Kent, OH, 44242, USA., Kim WY; Department of Biological Sciences, Kent State University, Kent, OH, 44242, USA. wkim2@kent.edu. |
| Abstrakt: |
Genetic evidence indicates that haploinsufficiency of ARID1B causes intellectual disability (ID) and autism spectrum disorder (ASD), but the neural function of ARID1B is largely unknown. Using both conditional and global Arid1b knockout mouse strains, we examined the role of ARID1B in neural progenitors. We detected an overall decrease in the proliferation of cortical and ventral neural progenitors following homozygous deletion of Arid1b, as well as altered cell cycle regulation and increased cell death. Each of these phenotypes was more pronounced in ventral neural progenitors. Furthermore, we observed decreased nuclear localization of β-catenin in Arid1b-deficient neurons. Conditional homozygous deletion of Arid1b in ventral neural progenitors led to pronounced ID- and ASD-like behaviors in mice, whereas the deletion in cortical neural progenitors resulted in minor cognitive deficits. This study suggests an essential role for ARID1B in forebrain neurogenesis and clarifies its more pronounced role in inhibitory neural progenitors. Our findings also provide insights into the pathogenesis of ID and ASD. |
