The use of genomewide ENU mutagenesis screens to unravel complex mammalian traits: identifying genes that regulate organ-specific and systemic autoimmunity

Authors

  • Gerard F. Hoyne,

    Corresponding author
    1. Australian Cancer Research Foundation Genetics Laboratory and Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia.
      * Gerard F. Hoyne
      Australian Cancer Research Foundation Genetics Laboratory and Australian Phenomics Facility
      John Curtin School of Medical Research
      Mills Road
      Australian National University
      Canberra ACT 2601
      Australia
      Tel.: +61 62 6125 2435
      Fax: +61 62 6125 4301
      E-mail: gerard.hoyne@anu.edu.au
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  • Christopher C. Goodnow

    1. Australian Cancer Research Foundation Genetics Laboratory and Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia.
    Search for more papers by this author

* Gerard F. Hoyne
Australian Cancer Research Foundation Genetics Laboratory and Australian Phenomics Facility
John Curtin School of Medical Research
Mills Road
Australian National University
Canberra ACT 2601
Australia
Tel.: +61 62 6125 2435
Fax: +61 62 6125 4301
E-mail: gerard.hoyne@anu.edu.au

Abstract

Summary:  T-cell development is perhaps one of the best understood processes of mammalian cell differentiation, as many of the genes and pathways have been identified. By contrast, relatively little is known about the genes and pathways involved in immunological tolerance to self-antigens. Here, we describe the challenges associated with a genomewide screen designed at identifying new immune regulatory genes that uses a model of organ-specific autoimmunity leading to type 1 diabetes. The successful propagation and identification of the new gene variants will shed light on the various developmental checkpoints in lymphocyte development that are crucial for establishing tolerance to self-antigens.

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