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Engineering a mouse balancer chromosome

Nature Genetics volume 22, pages 375–378 (1999)Cite this article

Abstract

Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens1. Despite their utility, balancer chromosomes are rarely used in mice because they are difficult to generate using conventional methods. Here we describe the engineering of a mouse balancer chromosome with the Cre-loxP recombination system. The chromosome features a 24-centiMorgan (cM) inversion between Trp53 (also known as p53) and Wnt3 on mouse chromosome 11 that is recessive lethal and dominantly marked with a K14-Agouti transgene2. When allelic to a wild-type chromosome, the inversion suppresses crossing over in the inversion interval, accompanied by elevated recombination in the flanking regions. The inversion functions as a balancer chromosome because it can be used to maintain a lethal mutation in the inversion interval as a self-sustaining trans-heterozygous stock. This strategy can be used to generate similar genetic reagents throughout the mouse genome. Engineering of visibly marked inversions and deficiencies is an important step toward functional analyses of the mouse genome and will facilitate large-scale mutagenesis programs.

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Figure 1: How a single crossover between a wild-type chromosome and a paracentric inversion (an inversion that does not span the centromere) leads to inviable dicentric and acentric products.
Figure 2: A three-step Cre-loxP–based strategy to engineer the Trp53-Wnt3 inversion.
Figure 3: Southern-blot analysis of the Trp53Brdm2 targeted allele, the Wnt3Brdm2 targeted allele and the Trp53-Wnt3 inversion.
Figure 4: Characterization of the Trp53-Wnt3 inversion.
Figure 5

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Acknowledgements

We thank H. Su for information on polymorphic markers used in assessing recombination frequencies; M. Suraokar for the Hoxb4r mouse line; S. Rivera and S. Vaishnav for preparing feeder cells; J. Weber for helpful discussions; and H. Bellen and M. Justice for helpful comments on the manuscript. This work was supported partly by grants from the National Institutes of Health and the U.S. Department of Defense. A.B. is an investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, Texas, USA

    Binhai Zheng, Marijke Sage, Wei-Wen Cai, Debrah M. Thompson, Yin-Chai Cheah & Allan Bradley

  2. Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, Texas, USA

    Debrah M. Thompson & Allan Bradley

  3. Developmental Biology Program, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, Texas, USA

    Beril C. Tavsanli & Allan Bradley

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  1. Binhai Zheng
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Correspondence to Allan Bradley.

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Zheng, B., Sage, M., Cai, WW. et al. Engineering a mouse balancer chromosome. Nat Genet 22, 375–378 (1999). https://doi.org/10.1038/11949

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