MOUSE GENE MANIPULATION CORE (CORE E) ABSTRACT The primary objective of the Mouse Gene Manipulation Core is to provide all our IDDRC investigators with a centralized, affordable and quality-controlled service, using state-of-the art genome editing technology, for the rapid and efficient generation of genetically altered mouse lines. Our goal is aid our PIs in their work on identifying the role of particular genes in the development of the nervous system and in modelling intellectual disability and neurodevelopmental disorders, with a view in particular of identifying preclinically, novel biomarkers of these disorders and for evaluating the efficacy of new therapeutic approaches. Although manipulation of the mouse genome has been well established for several decades using homologous combination in embryonic stem cells for gene targeting and random insertion of DNA in zygotes for making transgenic mice, and this Core has very effectively used these approaches to generate many mouse models of neurodevelopmental disorders, during the course of the present grant cycle transformative advances have been made in our capacity for genome editing. This core has enthusiastically embraced and mastered the new CRISPR/Cas9 technology for disrupting gene expression by base insertion/deletion (INDELS), and using homology directed repair (HDR) for introducing mutations, inserting reporters, Cre or Flp drivers and indeed making many kinds of changes to the genome ? in a manner that is both efficient and fast. We will continue to offer our standard technology since there are users and uses that favor this but anticipate that CRISPR/Cas9 and its evolution will largely take over. The technology has caused immense excitement in the IDDRC community and the demand for our services are set to increase substantially, so that the IDDRC can provide parallel preclinical and clinical phenotyping and efficacy studies. To aid in the uptake of genome editing the core will offer consultation services on the best approach for PIs to use for particular projects, advice on selection of guide RNAs, genotyping and colony management, as well as a new cryopreservation service. Collectively the new services will offer the IDDRC mouse models faster and cheaper with the capacity to preserve these for alter use or sharing.
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