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    Efficient generation and mapping of recessive developmental mutations using ENU mutagenesis

    Date
    2002
    Author
    Herron, Bruce J.
    Lu, Weining
    Rao, Cherie
    Liu, Shanming
    Peters, Heiko
    Bronson, Roderick T.
    Justice, Monica J.
    McDonald, J. David
    Beier, David R.
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    Citation
    Herron, Bruce J.; Lu, Weining; Rao, Cherie; Liu, Shanming; Peters, Heiko; Bronson, Roderick T.; Justice, Monica J.; McDonald, J. David; Beier, David R. 2002. Efficient generation and mapping of recessive developmental mutations using ENU mutagenesis. Nature Genetics, v.30 no.2 pp.185-189
    Abstract
    Treatment with N-ethyl-N-nitrosourea (ENU) efficiently generates single-nucleotide mutations in mice. Along with the renewed interest in this approach, much attention has been given recently to large screens with broad aims; however, more finely focused studies have proven very productive as well. Here we show how mutagenesis together with genetic mapping can facilitate the rapid characterization of recessive loci required for normal embryonic development. We screened third-generation progeny of mutagenized mice at embryonic day (E) 18.5 for abnormalities of organogenesis. We ascertained 15 monogenic mutations in the 54 families that were comprehensively analyzed. We carried out the experiment as an outcross, which facilitated the genetic mapping of the mutations by haplotype analysis. We mapped seven of the mutations and identified the affected locus in two lines. Using a hierarchical approach, it is possible to maximize the efficiency of this analysis so that it can be carried out easily with modest infrastructure and resources.
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    URI
    http://dx.doi.org/10.1038/ng812
    http://hdl.handle.net/10057/5634
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