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Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors

By Yuen Gao, Natalia Duque-Wilckens, Mohammad B. Aljazi, Yan Wu, Adam J. Moeser,George I. Mias, Alfred J. Robison & Jin He

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Here the researchers show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. This study establishes an ASD/ID mouse model (Ash1L knockout mouse model) revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities. The study includes: 

  • Generation and characterization of Ash1L knockout mice

  • Loss of ASH1L delays embryonic and postnatal brain development

  • Loss of ASH1L in the developing mouse brain causes ASD/ID like behaviors

  • Loss of ASH1L impairs expression of genes critical for brain development