Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development.

Journal Article (Journal Article)

Males with X-linked severe combined immunodeficiency (XSCID) have defects in the common cytokine receptor gamma chain (gamma c) gene that encodes a shared, essential component of the receptors of interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15. The Janus family tyrosine kinase Jak3 is the only signaling molecule known to be associated with gamma c, so it was hypothesized that defects in Jak3 might cause an XSCID-like phenotype. A girl with immunological features indistinguishable from those of XSCID was therefore selected for analysis. An Epstein-Barr virus (EBV)-transformed cell line derived from her lymphocytes had normal gamma c expression but lacked Jak3 protein and had greatly diminished Jak3 messenger RNA. Sequencing revealed a different mutation on each allele: a single nucleotide insertion resulting in a frame shift and premature termination in the Jak3 JH4 domain and a nonsense mutation in the Jak3 JH2 domain. The lack of Jak3 expression correlated with impaired B cell signaling, as demonstrated by the inability of IL-4 to activate Stat6 in the EBV-transformed cell line from the patient. These observations indicate that the functions of gamma c are dependent on Jak3 and that Jak3 is essential for lymphoid development and signaling.

Full Text

Duke Authors

Cited Authors

  • Russell, SM; Tayebi, N; Nakajima, H; Riedy, MC; Roberts, JL; Aman, MJ; Migone, TS; Noguchi, M; Markert, ML; Buckley, RH; O'Shea, JJ; Leonard, WJ

Published Date

  • November 3, 1995

Published In

Volume / Issue

  • 270 / 5237

Start / End Page

  • 797 - 800

PubMed ID

  • 7481768

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.270.5237.797


  • eng

Conference Location

  • United States