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

Fernando Benavides, Ann Venables, Heather Poetschke Klug, Edward Glasscock, Alexander Rudensky, Marcela Gómez, Natalia Martin Palenzuela, Jean Louis Guénet, Ellen R. Richie, Claudio J. Conti

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)233-242
Number of pages10
Issue number3
StatePublished - 2001


  • CD4 deficiency
  • Cathepsin L
  • Hair loss mutation
  • Laboratory mouse
  • T-cell selection

ASJC Scopus subject areas

  • Immunology
  • Genetics


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