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  • Title: The scid defect affects the final step of the immunoglobulin VDJ recombinase mechanism.
    Author: Malynn BA, Blackwell TK, Fulop GM, Rathbun GA, Furley AJ, Ferrier P, Heinke LB, Phillips RA, Yancopoulos GD, Alt FW.
    Journal: Cell; 1988 Aug 12; 54(4):453-60. PubMed ID: 3135938.
    Abstract:
    Abelson murine leukemia virus-transformed precursor B lymphocytes from scid (severe combined immunodeficient) mice, like A-MuLV transformants from normal mice, actively rearrange segments of their Ig heavy chain variable region gene locus during growth in culture. Targeting of recombination to appropriate segments appears normal in these lines as evidenced by initial rearrangement of sequences from within the D and JH locus to form aberrant "DJH" rearrangements and secondary rearrangement of sequences from within the VH locus to the aberrant "DJH" intermediates. A detailed analysis of the joints in these rearrangements indicates that the VDJ recombinase in scid pre-B cells can correctly recognize heptamernonamer signal sequences and perform precise endonucleolytic scissions at these sequences. We propose that the scid defect involves the inability of scid precursor lymphocytes to join correctly the cleaved ends of the coding strands of variable region gene segments.
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