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X-ray-induced deletion complexes in embryonic stem cells on mouse chromosome 15

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Abstract

Chromosomal deletions have long been used as genetic tools in dissecting the functions of complex genomes, and new methodologies are still being developed to achieve the maximum coverage. In the mouse, where the chromosomal deletion coverage is far less extensive than that in Drosophila, substantial coverage of the genome with deletions is strongly desirable. This article reports the generation of three deletion complexes in the distal part of mouse Chromosome (Chr) 15. Chromosomal deletions were efficiently induced by X rays in embryonic stem (ES) cells around the Otoconin 90 (Oc90), SRY-box-containing gene 10 (Sox10), and carnitine palmitoyltransferase 1b (Cpt1b) loci. Deletions encompassing the Oc90 and Sox10 loci were transmitted to the offspring of the chimeric mice that were generated from deletion-bearing ES cells. Whereas deletion complexes encompassing the Sox10 and the Cpt1b loci overlap each other, no overlap of the Oc90 complex with the Sox10 complex was found, possibly indicating the existence of a haploinsufficient gene located between Oc90 and Sox10. Deletion frequency and size induced by X rays depend on the selective locus, possibly reflecting the existence of haplolethal genes in the vicinity of these loci that yield fewer and smaller deletions. Deletions induced in ES cells by X rays vary in size and location of breakpoints, which makes them desirable for mapping and for functional genomics studies.

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Acknowledgments

The authors thank Dr. Terry Magnuson for his advice about the ES cell derivation experiment and Dr. Karen Moore for a list of polymorphic markers between B6 and 129. We appreciate Dr. Liane Russell for her critical review of the manuscript. This project was supported by the Office of Biological and Environmental Research, U.S. Department of Energy, under contract DE-AC05-00OR22725 with UT-Battelle, LLC.

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Authors and Affiliations

  1. Graduate School of Genome Sciences and Technology, The University of Tennessee, Knoxville, Tennessee, 37996, USA

    Wallace S.H. Chick

  2. Mammalian Genetics and Genomics Group, Life Sciences Division, Oak Ridge National Laboratory, P.O. Box 2008, Bethel Valley Road, Building 1061, Room 206, Oak Ridge, Tennessee, 37831, USA

    Sarah E. Mentzer, Donald A. Carpenter, Dabney Johnson & Yun You

  3. Department of Biochemistry, Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee, 37996, USA

    Eugene M. Rinchik

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  1. Wallace S.H. Chick
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  2. Sarah E. Mentzer
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Correspondence to Yun You.

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Chick, W.S., Mentzer, S.E., Carpenter, D.A. et al. X-ray-induced deletion complexes in embryonic stem cells on mouse chromosome 15. Mamm Genome 16, 661–671 (2005). https://doi.org/10.1007/s00335-005-0011-5

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