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Towards a transgenic marmoset model for neurodevelopmental disorders - Alexander Urban

Stanford Neurosciences Institute, Alexander Urban
October 31, 2017 - 10:50am to 11:20am
James Clark Auditorium

Towards a transgenic marmoset model for neurodevelopmental disorders

Alexander Urban

Assistant Professor of Psychiatry and Behavioral Sciences and of Genetics 

2015 Seed Grant: Creating an advanced transgenic animal model of autism

Lead Researcher(s): Karen ParkerAlexander UrbanMegan AlbertelliJoachim Hallmayer


 Our goal is to create transgenic marmosets with large copy number variants (CNVs) in their genomes that are syntenic to large CNVs in humans, and which are strongly associated with neurodevelopmental and neuropsychiatric disorders (e.g., autism, schizophrenia). Such marmoset models are expected to be beneficial in this context for approaches such as behavioral testing and drug screening as well as elucidating the neuronal circuits involved in these disorders. As a first step towards this goal, we have acquired a marmoset embryonic stem cell line and have thoroughly characterized it. This has included testing for pluripotency and differentiation potential, as well as assessing the cell line’s ability to be used in conjunction with the CRISPR genome editing approach. We have also carried out whole-genome sequencing on this marmESC line, including using virtual-long-reads to phase the genome sequence into its haplotypes. This allowed us to produce a haplotype-specific CRISPR targeting map, which in turn will enable us to make two widely separated cuts on one and the same haplotype (i.e. just cutting on either the maternal or just the paternal copy of a given chromosome), as a critical prerequisite for the engineering of large CNVs. This marmESC line can now be used for the CNV engineering, to then either be directly introduced into a marmoset embryo, or as a system for testing engineering vectors that can be directly injected into early marmoset embryos.

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Stanford Neurosciences Institute
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