The CD4 T cell-deficient mouse mutation nackt (nkt) involves a deletion in the cathepsin L (Ctsl) gene (original) (raw)

Abstract.

We recently reported a novel autosomal recessive mouse mutation designated nackt (nkt). Homozygous mutant mice have diffuse alopecia and a marked reduction in the proportion of CD4+ T cells in the thymus and peripheral lymphoid tissues. Here we show that the CD4 T-cell deficiency is due to a defect in the thymic microenvironment rather than the hematopoietic compartment. Furthermore, we identified the molecular basis of the mutant phenotype by demonstrating that the nkt mutation represents a 118-bp deletion of the cathepsin L (Ctsl) gene which is required for degradation of the invariant chain, a critical chaperone for major histocompatibility complex class II molecules. This finding explains the similarities in skin and immune defects observed in nkt/nkt and Ctsl –/– mice. The data reported here provide further in vivo evidence that the lysosomal cysteine protease cathepsin L plays a critical role in CD4+ T-cell selection in the thymus.

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Authors and Affiliations

  1. Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Park Road 1C, P.O. Box 389, Smithville, TX 78957, USA, , , , ,
    Fernando Benavides, Ann Venables, Heather Poetschke Klug, Edward Glasscock, Ellen R. Richie & Claudio J. Conti
  2. Unité de Génétique des Mammifères, Institut Pasteur, 25 rue du Docteur Roux 75724 Paris, Cedex 15, France, , , , ,
    Natalia Martin Palenzuela & Jean-Louis Guénet
  3. Howard Hughes Medical Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA, , , , ,
    Alexander Rudensky & Marcela Gómez

Authors

  1. Fernando Benavides
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  2. Ann Venables
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  3. Heather Poetschke Klug
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  4. Edward Glasscock
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  5. Alexander Rudensky
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  6. Marcela Gómez
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  7. Natalia Martin Palenzuela
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  8. Jean-Louis Guénet
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  9. Ellen R. Richie
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  10. Claudio J. Conti
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Benavides, F., Venables, A., Poetschke Klug, H. et al. The CD4 T cell-deficient mouse mutation nackt (nkt) involves a deletion in the cathepsin L (Ctsl) gene.Immunogenetics 53, 233–242 (2001). https://doi.org/10.1007/s002510100320

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