Efficient generation and mapping of recessive developmental mutations using ENU mutagenesis.
Document Type
Article
Publication Date
2002
Keywords
Base-Sequence, Chromosome-Mapping, DNA, DNA-Mutational-Analysis, Ethylnitrosourea, Female, Fetal-Development, Genes-Recessive, Haplotypes, Male, Mice, Mice-Inbred-A, Mice-Inbred-BALB-C, Mutagenesis, Mutation, Phenotype, Pregnancy, SUPPORT-U-S-GOVT-P-H-S
First Page
185
Last Page
189
JAX Source
Nat Genet 2002 Feb; 30(2):185-9.
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.
Recommended Citation
Herron BJ,
Lu W,
Rao C,
Liu S,
Peters H,
Bronson RT,
Justice MJ,
McDonald JD,
Beier DR.
Efficient generation and mapping of recessive developmental mutations using ENU mutagenesis. Nat Genet 2002 Feb; 30(2):185-9.