Abstract
Now that the mouse and human genome sequences are complete, biologists need systematic approaches to determine the function of each gene1,2. 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 diseases3. 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 chromosomes6. 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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Acknowledgements
We thank C. Viator, C. Dinh, S. Moncrief, A. Zalud, J. Maffucci, C. Mason-Garrison, K. Firozi, M. Alviento, C. Hubbard, B. Hasson and M. Scantlin for technical assistance, and J. Zhong and M. Patterson for database support. We also thank L. Peters for the gift of Slc4a1 knockout mice. Y. Furuta, H. Bellen, S. Lovell, S. Watowich and H. Gilbert are thanked for critical reading of this manuscript. This work was supported by NIH grants to M.J.J. and A.B. K.E.H. was supported by an NIH-NRSA grant. B.T.K. is a Fellow of the Leukemia Research Foundation.
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Supplementary information
41586_2003_BFnature01865_MOESM1_ESM.xls
Supplementary Table 1: A complete list of mutations isolated throughout the genome, a short phenotype description, and map location if known. (XLS 27 kb)
41586_2003_BFnature01865_MOESM7_ESM.ppt
Supplementary Figure 2: Additional photos of l11Jus3, l11Jus27, and three mutations classified as having neural tube defects: l11Jus8, l11Jus15, and l11Jus39. (PPT 5756 kb)
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Kile, B., Hentges, K., Clark, A. et al. Functional genetic analysis of mouse chromosome 11. Nature 425, 81–86 (2003). https://doi.org/10.1038/nature01865
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DOI: https://doi.org/10.1038/nature01865
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