Nature of the Defect in the Scid Mouse Mutant
Early B and T lymphocyte differentiation appears to be arrested in C.B-17/Icr scid/scid mice (Bosma et al. 1983), a mutant mouse strain homozygous for an autosomal recessive mutation (scid) on chromosome 16 (Bosma et al. 1989). Though developing B and T lymphocytes in these mice (hereafter referred to as scid mice) reach the stage at which immunoglobulin heavy (Igh) chain genes and T cell receptor (TCR) β and γ genes become transcriptionally active (Schuler et al. 1988), cells with Igh or TCRβ and TCRγ rearrangements have not been directly detected in scid lymphopoietic tissues (Schuler et al. 1986). The only indication that early Scid lymphocytes attempt Igh or TCR rearrangements has come from findings of abnormal antigen receptor gene rearrangements in transformed scid lymphocytes (Schuler et al. 1986; Lieber et al. 1988; Malynn et al. 1988; Hendrickson et al. 1988; Kim et al. 1988) and in early B cells recovered from long-term cultures of scid bone marrow cells (Okazaki et al. 1988). For example, infection of scid bone marrow cells with Abelson murine leukemia virus (A-MuLV) results in the recovery of transformed pre-B cells with abnormal Igh rearrangements, even though such cells cannot be detected by fluorescent activated cell sorter (FACS) analysis of scid bone marrow cells. To explain the apparent paucity of these cells and their abnormal Igh rearrangements, it was hypothesized (Schuler et al. 1986) that they die prematurely as a result of a defective recombinase system; transformation would thus serve to immortalize early scid lymphocytes before they die. This hypothesis recently received added support from more detailed analyses showing that transformed, immature scid lymphocytes have an active, but abnormal VDJ recombinase activity which is unable to catalyze with appreciable frequency the formation of functional V(D)J coding joints (Lieber et al. 1988; Malynn et al 1988).
KeywordsScid Mouse Severe Combine Immune Deficiency Fluorescence Activate Cell Sorter Analysis Recombination Fragment Autosomal Recessive Mutation
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