Complementation of V(D)J recombination defect and X-ray sensitivity of scid mouse cells by human chromosome 8.
Cells derived from mice homozygous for the severe combined immune deficiency (scid) mutation exhibit hypersensitivity to ionizing radiation, and defects in DNA double-strand break repair and V(D)J recombination. Using the technique of microcell-mediated chromosome transfer, we have introduced a number of dominantly marked human chromosomes into scid cells to localize the human homolog of the murine scid gene. Analysis of human-scid hybrid clones revealed that the presence of human chromosome 8 partially restored accurate V(D)J recombination and radioresistance to scid cells. Subsequent loss of the human chromosome 8 from human-scid hybrid clones rendered these cells sensitive to gamma-radiation and impaired their ability to catalyse V(D)J recombination. Introduction of chromosomes 2, 14, 16 and 19 that encode other repair genes did not result in the correction of these two scid defects. These observations demonstrate that the human homolog of the mouse scid gene resides on human chromosome 8.
Banga
S S
SS
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2757.
Hall
K T
KT
Sandhu
A K
AK
Weaver
D T
DT
Athwal
R S
RS
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D005720:Gamma Rays; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D018014:Gene Transfer Techniques; D005816:Genetic Complementation Test; D006801:Humans; D006822:Hybrid Cells; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D011836:Radiation Tolerance / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics* / Q000528:radiation effects
D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region