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Genetic and Molecular Quality Control of Genetically Engineered Mice

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Transgenesis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2631))

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Abstract

Genetically engineered mice are used as avatars to understand mammalian gene function and develop therapies for human disease. During genetic modification, unintended changes can occur, and these changes may result in misassigned gene-phenotype relationships leading to incorrect or incomplete experimental interpretations. The types of unintended changes that may occur depend on the allele type being made and the genetic engineering approach used. Here we broadly categorize allele types as deletions, insertions, base changes, and transgenes derived from engineered embryonic stem (ES) cells or edited mouse embryos. However, the methods we describe can be adapted to other allele types and engineering strategies. We describe the sources and consequ ences of common unintended changes and best practices for detecting both intended and unintended changes by screening and genetic and molecular quality control (QC) of chimeras, founders, and their progeny. Employing these practices, along with careful allele design and good colony management, will increase the chance that investigations using genetically engineered mice will produce high-quality reproducible results, to enable a robust understanding of gene function, human disease etiology, and therapeutic development.

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Acknowledgments

The authors would like to thank their colleagues at The Centre for Phenogenomics for their assistance with implementing the assays described in this manuscript. The authors received salary support funding from Genome Canada and Ontario Genomics OGI-137 and the Canada Foundation for Innovation Major Science Initiatives (MSI) Fund 35534. Figures were created with BioRender.com.

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Authors and Affiliations

  1. The Centre for Phenogenomics, Toronto, ON, Canada

    Lauri G. Lintott & Lauryl M. J. Nutter

  2. The Hospital for Sick Children, Toronto, ON, Canada

    Lauri G. Lintott & Lauryl M. J. Nutter

Authors
  1. Lauri G. Lintott
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  2. Lauryl M. J. Nutter
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Corresponding author

Correspondence to Lauryl M. J. Nutter .

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Editors and Affiliations

  1. Transgenic Animal Model Core, University of Michigan, Ann Arbor, MI, USA

    Thomas L. Saunders

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Lintott, L.G., Nutter, L.M.J. (2023). Genetic and Molecular Quality Control of Genetically Engineered Mice. In: Saunders, T.L. (eds) Transgenesis. Methods in Molecular Biology, vol 2631. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2990-1_3

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  • DOI: https://doi.org/10.1007/978-1-0716-2990-1_3

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2989-5

  • Online ISBN: 978-1-0716-2990-1

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