The use of genomewide ENU mutagenesis screens to unravel complex mammalian traits: identifying genes that regulate organ-specific and systemic autoimmunity.
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.
Hoyne
Gerard F
GF
Australian Cancer Research Foundation Genetics Laboratory and Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia. gerard.hoyne@anu.edu.au
Goodnow
Christopher C
CC
D000818:Animals; D015551:Autoimmunity / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005038:Ethylnitrosourea / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D005820:Genetic Testing / Q000379:methods*; D016678:Genome / Q000187:drug effects* / Q000235:genetics; D023281:Genomics; D006801:Humans; D051379:Mice; D016296:Mutagenesis; D013601:T-Lymphocytes / Q000276:immunology
D005038:Ethylnitrosourea