8 research outputs found
Three Novel Pigmentation Mutants Generated by Genome-Wide Random ENU Mutagenesis in the Mouse
Three mutant mice with pigmentation phenotypes were recovered from a genomewide
random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986),
Belly spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2;
MGI:1861991) were identified following visual inspection of progeny from a male
exposed to the point mutagen ethylnitrosourea (ENU). In order to rapidly localize
the causative mutations, genome-wide linkage scans were performed on pooled
DNA samples from backcross animals for each mutant line. Whto was mapped to
proximal mouse chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112
(8.0 cM from the centromere), Bswt was mapped to centric Mmul between D1Mit214
(32.1 cM) and D1Mit480 (32.8 cM) and Dfp2 was mapped to proximalMmu4 between
Cen and D4Mit18 (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting
points in furthering the elucidation of genetic and biochemical pathways relevant
to pigmentation and associated biological processes
Primary non-random X-inactivation caused by controlling elements in the mouse demonstrated at the cellular level
The Pro-115 Gln mutation in peroxisome-proliferator-activated receptor (PPAR) γ2 is extremely rare in a large cohort of U.S. Caucasians
The Pro-115 → Gln mutation in peroxisome-proliferator-activated receptor (PPAR) γ2 is extremely rare in a large cohort of U.S. Caucasians
A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse
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