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

Journal Article · Fri Feb 15 04:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.88.4.1394· OSTI ID:5891757

Biedermann, K A; Sun, J R; Giaccia, A J; Tosto, L M; Brown, J M ^[1]

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1. Stanford Univ. Medical Center, CA (USA)

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.

• OSTI ID: 5891757
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 88:4; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BLEOMYCIN
CELL KILLING
CONNECTIVE TISSUE CELLS
DNA REPAIR
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTROMAGNETIC RADIATION
ELECTROPHORESIS
FIBROBLASTS
GAMMA RADIATION
GENE MUTATIONS
IMMUNITY
IONIZING RADIATIONS
MAMMALS
MICE
MUTATIONS
RADIATIONS
RADIOSENSITIVITY
RECESSIVE MUTATIONS
RECOVERY
REPAIR
RODENTS
SOMATIC CELLS
STEM CELLS
STRAND BREAKS
VERTEBRATES