Nature of the Defect in the Scid Mouse Mutant

  • M. J. Bosma
  • M. Fried
  • R. R. Hardy
  • A. M. Carroll


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).


Scid Mouse Severe Combine Immune Deficiency Fluorescence Activate Cell Sorter Analysis Recombination Fragment Autosomal Recessive Mutation 
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  1. Arp B, McMullen MD, Storb U (1982) Sequence of immunoglobulin λl genes in a λI defective mouse strain. Nature 298: 184–186PubMedCrossRefGoogle Scholar
  2. Bosma GC, Custer RP, Bosma MJ (1983) A severe combined immune immunodeficiency mutation in the mouse. Nature 301: 527–530PubMedCrossRefGoogle Scholar
  3. Bosma GC, Davisson MT, Ruetsch NR, Sweet HO, Shultz LD, Bosma MJ (1989) The mouse mutation severe combined immune deficiency (scid) is on chromosome 16. Immunogenetics 29: 54–57PubMedCrossRefGoogle Scholar
  4. Carroll AM, Bosma MJ (1989) Rearrangement of T cell receptor delta genes in thymus of scid mice. Current Topics in Microbiology and Immunology (in press)Google Scholar
  5. Chien Y, Iwashima M, Kaplan KB, Elliott JF, Davis MM (1987a) A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. Nature 327: 677–682PubMedCrossRefGoogle Scholar
  6. Chien Y, Iwashima M, Wettstein DA, Kaplan KB, Elliott JF, Born W, Davis MM (1987b) T-cell receptor 8 gene rearrangements in early thymocytes. Nature 330: 722–727PubMedCrossRefGoogle Scholar
  7. Elliott JF, Rock EP, Patten PA, Davis MM, Chien Y (1988) The adult T-cell receptor S-chain is diverse and distinct from that of fetal thymocytes. Nature 331: 627–631PubMedCrossRefGoogle Scholar
  8. Epstein R, Davisson M, Lehmann K, Akeson EC, Cohn M (1986) Position of Igl-1 md, and Bst loci on chromosome 16 of the mouse. Immunogenetics 23: 78–83PubMedCrossRefGoogle Scholar
  9. Fried M, Hardy RR, Bosma MJ (1989) Differentiation of B-lineage lymphocytes in immunoglobulin transgenic scid mice, (submitted)Google Scholar
  10. Grosschedl R, Weaver D, Baltimore D, Costantini F (1984) Introduction of a µ1 immunoglobulin gene into the mouse germline: specific expression in lymphoid cells and synthesis of functional antibody. Cell 38: 647–658PubMedCrossRefGoogle Scholar
  11. Hendrickson EA, Schatz DG, Weaver DT (1988) The scid gene encodes a transacting factor that mediates the rejoining event of Ig gene rearrangement. Genes Dev 2: 817–829PubMedCrossRefGoogle Scholar
  12. Kim MG, Schuler W, Bosma MJ, Marcu KB (1988) Abnormal recombination of Igh D and J gene segments in transformed pre-B cells of scid mice. J Immunol 141: 1341–1347PubMedGoogle Scholar
  13. Lieber MR, Hesse JE, Lewis S, Bosma GC, Rosenberg N, Mizuuchi K, Bosma MJ, Geliert M (1988) The defect in murine severe combined immune deficiency: joining of signal sequences but not coding segments in V(D)J recombination. Cell 55: 7–16.PubMedCrossRefGoogle Scholar
  14. Malynn BA, Blackwell TK, Fulop GM, Rathbun GA, Furley AJW, Ferner P, Heinke LB, Phillips RA, Yancopoulis GD, Alt FW (1988) The scid defect effects the final step of the immunoglobulin VDJ recombinase mechanism. Cell 54: 453–460PubMedCrossRefGoogle Scholar
  15. Okazaki K, Nishikawa SI, Sakano H (1988) Aberrant immunoglobulin gene rearrangement in scid mouse bone marrow cells. J Immunol 141: 1348–1352PubMedGoogle Scholar
  16. Schuler W, Weiler IJ, Schüler A, Phillips RA, Rosenberg N, Mak TW, Kearney JF, Perry RP, Bosma MJ (1986) Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell 46: 963–972PubMedCrossRefGoogle Scholar
  17. Schuler W, Schuler A, Lennon GG, Bosma GC, Bosma MJ (1988) Transcription of unrearranged antigen receptor genes in scid mice. EMBO J 7: 2019–2024PubMedCentralPubMedGoogle Scholar
  18. Storb U, Pinkert C, Arp B, Engler P, Gollahon K, Manz J, Brady W, Brinster RL (1986) Transgenic mice with µ and k genes encoding anti-phosphorylcholine antibodies. J Exp Med 164: 627–641PubMedCrossRefGoogle Scholar
  19. Tidmarsh GF, Heimfeld S, Whitlock CA, Weissman IL, Müller-Sieburg CE (1989) Identification of a novel bone marrow derived B cell progenitor population which coexpresses B220 and Thy-1 and is highly enriched for Abelson leukemia virus targets. Mol Cell Biol 9: 2665–2671PubMedCentralPubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • M. J. Bosma
  • M. Fried
  • R. R. Hardy
  • A. M. Carroll

There are no affiliations available

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