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Translational Assessments in Two Genetic Preclinical Models of Disrupted Chromatin Processes: Development and Motor Outcomes

Poster Presentation

Friday, May 3, 2019: 11:30 AM-1:30 PM

Room: 710 (Palais des congres de Montreal)

S. Petkova1, C. P. Canales2, A. S. Nord3, J. Ellegood4, J. P. Lerch4 and J. L. Silverman5, (1)MIND Institute and Department of Psychiatry and Behavioral Sciences, Sacramento, CA, (2)Center for Neuroscience | MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis, Davis, CA, (3)Center for Neuroscience, Department of Neurobiology, Physiology, & Behavior, University of California, Davis, Davis, CA, (4)Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada, (5)MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA

Background:

Numerous genes related to chromatin modification processes are among the top autism -associated risk genes, including AT-Interactive Domain 1B (ARID1B) and Chromodomain-Helicase DNA Binding Protein 8 (CHD8) (Cook & Scherer, 2008, O’Roak & State, 2008, O Roak 2014, Lossifov 2014, Werling 2018). These two candidate genes have related functional activities albeit act via differential pathways: ARID1B is a SWI/SNF complex protein in neuronal BAF chromatin complexes, and CHD8 encodes an ATP-dependent chromatin helicase.

Objectives:

To examine developmental outcomes such as physical growth and neurological reflexes in two preclinical models of genetically defined ASD.

To focus on motor as a key domain because: a) there is a strong correlation between motor and social communication, b) there is a strong correlation between motor skills and assessment of cognitive abilities, and c) motor is highly translatable between preclinical models and human studies.