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The Genome Editing Core (GEC) provides DRC investigators with resources to manipulate the genome of laboratory mice with the aim of studying the genetics underlying diabetes and its complications. The GEC maintains a facility for the generation of transgenic mouse models to aid in studying the genetic mechanisms underlying diabetes in vivo. The mouse modeling facility uses CRISPR/Cas9 constructs to introduce genome modifications to a variety of mouse lines in order to establish new models of the disease within a living mammalian system.
This Core enables investigators to manipulate the genome of laboratory mice in order to generate the most relevant experimental models to understand the genetics and mechanisms underlying diabetes and its complications. The GEC blends Joslin's research expertise in mouse models for diabetes and the generation of genetically modified mice.
The GEC will support the production of genetically modified mice, tailored to investigators' experimental questions by performing pronuclear and intracytoplasmic microinjections. If necessary, the Core can also provide lentiviral transgenesis services for generating mice that carry transgenes mediating inducible or constitutive silencing of target genes of interest by RNAi. The primary method of genetic modification is the CRISPR/Cas9 complex.
The Core will perform mouse genome editing using a variety of targeted edits made possible through CRISPR/Cas9. This includes creating knockout mice by generating a random mutation following a double stranded break (DSB) and non-homologous endpoint joining (NHEJ). For more specific modifications, the use of DNA templates can effect sequence insertion or replacement for knock-in models, for example. Other methods of influencing gene activation or repression are available and can be used upon request.
For questions about the GE Core and its CRISPR modified mice services, please contact Taylor Roberts (Taylor.Roberts@joslin.harvard.edu) or Stephan Kissler (Stephan.Kissler@joslin.harvard.edu).
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