Functional genetic analysis of mouse chromosome 11.
Now that the mouse and human genome sequences are complete, biologists need systematic approaches to determine the function of each gene. A powerful way to discover gene function is to determine the consequence of mutations in living organisms. Large-scale production of mouse mutations with the point mutagen N-ethyl-N-nitrosourea (ENU) is a key strategy for analysing the human genome because mouse mutants will reveal functions unique to mammals, and many may model human diseases. To examine genes conserved between human and mouse, we performed a recessive ENU mutagenesis screen that uses a balancer chromosome, inversion chromosome 11 (refs 4, 5). Initially identified in the fruitfly, balancer chromosomes are valuable genetic tools that allow the easy isolation of mutations on selected chromosomes. Here we show the isolation of 230 new recessive mouse mutations, 88 of which are on chromosome 11. This genetic strategy efficiently generates and maps mutations on a single chromosome, even as mutations throughout the genome are discovered. The mutations reveal new defects in haematopoiesis, craniofacial and cardiovascular development, and fertility.
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