scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair - PubMed (original) (raw)

scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair

K A Biedermann et al. Proc Natl Acad Sci U S A. 1991.

Abstract

C.B-17 severe combined immunodeficient (scid) mice carry the scid mutation and are severely deficient in both T cell- and B cell-mediated immunity, apparently as a result of defective V(D)J joining of the immunoglobulin and T-cell receptor gene elements. In the present studies, we have defined the tissue, cellular, and molecular basis of another characteristic of these mice: their hypersensitivity to ionizing radiation. Bone marrow stem cells, intestinal crypt cells, and epithelial skin cells from scid mice are 2- to 3-fold more sensitive when irradiated in situ than are congenic BALB/c or C.B-17 controls. Two independently isolated embryo fibroblastic scid mouse cell lines display similar hypersensitivities to gamma-rays. In addition, these cell lines are sensitive to cell killing by bleomycin, which also produces DNA strand breaks, but not by the DNA crosslinking agent mitomycin C or UV irradiation. Measurement of the rejoining of gamma-ray-induced DNA double-strand breaks by pulsed-field gel electrophoresis indicates that these animals are defective in this repair system. This suggests that the gamma-ray sensitivity of the scid mouse fibroblasts could be the result of reduced repair of DNA double-strand breaks. Therefore, a common factor may participate in both the repair of DNA double-strand breaks as well as V(D)J rejoining during lymphocyte development. This murine autosomal recessive mutation should prove extremely useful in fundamental studies of radiation-induced DNA damage and repair.

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References

1. 1. Nature. 1982 Jun 3;297(5865):402-4 - PubMed
2. 1. Cell. 1989 Dec 22;59(6):1035-48 - PubMed
3. 1. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2684-8 - PubMed
4. 1. Genes Dev. 1988 Jul;2(7):817-29 - PubMed
5. 1. Mutat Res. 1987 Jul-Aug;191(3-4):163-9 - PubMed

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