The scid gene encodes a trans-acting factor that mediates the rejoining event of Ig gene rearrangement.

Homozygous mutation at the scid locus in the mouse impairs lymphoid development and results in animals deficient in B and T cells. We found that immunoglobulin heavy-chain gene rearrangement was blocked at the D-JH stage in Abelson-transformed scid pre-B cell lines. Examination of the recombinational junctions indicated that the correct gene elements (D and JH) were assembled, as shown by the presence of D region and JH-region DNA on the breakpoint restriction fragments cloned from the genome of the scid cell lines. All rearrangement events were accompanied by deletions of varying sizes such that none of the rearrangements resulted in the production of functional immunoglobulins. The breakpoints of the rearrangement events did not correspond to the utilization of a novel heptamer-nonamer recombination signal but probably arose by nonspecific deletion from distal JH and D heptamer-nonamer signals in the process of recombination. scid pre-B cell lines were infected with a recombinant retrovirus (DGR) containing Ig joining signals. Aberrant rearrangements were observed in DGR DNA that was integrated randomly throughout the mouse genome, which suggested that the mutation in scid mice encodes a trans-acting factor that is part of the lymphoid gene recombination machinery.

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