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As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics.

Original publication

DOI

10.1038/78140

Type

Journal article

Journal

Nat Genet

Publication Date

08/2000

Volume

25

Pages

440 - 443

Keywords

Animals, Animals, Newborn, Chromosome Mapping, Crosses, Genetic, Cryopreservation, Ethylnitrosourea, Female, Fertilization in Vitro, Genes, Genome, Hematologic Tests, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Motor Activity, Mutagenesis, Mutagens, Mutation, Phenotype, Time Factors, Weaning