Random mutagenesis of proximal mouse chromosome 5 uncovers predominantly embryonic lethal mutations

被引:50
作者
Wilson, L
Ching, YH
Farias, M
Hartford, SA
Howell, G
Shao, HG
Bucan, M
Schimenti, JC
机构
[1] Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14853 USA
[2] Jackson Lab, Bar Harbor, ME 04609 USA
[3] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA
关键词
D O I
10.1101/gr.3826505
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A region-specific ENU mutagenesis screen was conducted to elucidate the functional content of proximal mouse Chr S. We used the visibly marked, recessive, lethal inversion RUMP White (Rw) as a balancer in a three-generation breeding scheme to identify recessive mutations within the -50 megabases spanned by Rw. A total of 1003 pedigrees were produced, representing the largest inversion screen performed in mice. Test-class animals, homozygous for the ENU-mutagenized proximal Chr 5 and visibly distinguishable from nonhomozygous littemates, were screened for fertility, hearing, vestibular function, DNA repair, behavior, and dysmorphology. Lethals were identifiable by failure to derive test-class animals within a pedigree. Embryonic lethal mutations (total of 34) were overwhelmingly the largest: class of mutants recovered. We characterized them with respect to the time of embryonic death, revealing that most act at midgestation (8.5-10.5) or sooner. To position the mutations within the Rw region and to guide allelism tests, we performed complementation analyses with a set of new and existing chromosomal deletions, as well as standard recombinational mapping on a Subset of the mutations. By pooling the data from this and other region-specific mutagenesis projects, we calculate that the mouse genome contains -3479-4825 embryonic lethal genes, or about 13.7%-19% of all genes.
引用
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页码:1095 / 1105
页数:11
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