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

Publication ,  Journal Article
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 in: Science
November 3, 1995

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.

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Published In

Science

DOI

ISSN

0036-8075

Publication Date

November 3, 1995

Volume

270

Issue

5237

Start / End Page

797 / 800

Location

United States

Related Subject Headings

  • X Chromosome
  • Trans-Activators
  • T-Lymphocytes
  • Signal Transduction
  • Severe Combined Immunodeficiency
  • STAT6 Transcription Factor
  • Receptors, Interleukin
  • RNA, Messenger
  • Protein-Tyrosine Kinases
  • Point Mutation
 

Citation

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Russell, S. M., Tayebi, N., Nakajima, H., Riedy, M. C., Roberts, J. L., Aman, M. J., … Leonard, W. J. (1995). Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science, 270(5237), 797–800. https://doi.org/10.1126/science.270.5237.797
Russell, S. M., N. Tayebi, H. Nakajima, M. C. Riedy, J. L. Roberts, M. J. Aman, T. S. Migone, et al. “Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development.Science 270, no. 5237 (November 3, 1995): 797–800. https://doi.org/10.1126/science.270.5237.797.
Russell SM, Tayebi N, Nakajima H, Riedy MC, Roberts JL, Aman MJ, et al. Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science. 1995 Nov 3;270(5237):797–800.
Russell, S. M., et al. “Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development.Science, vol. 270, no. 5237, Nov. 1995, pp. 797–800. Pubmed, doi:10.1126/science.270.5237.797.
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. Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science. 1995 Nov 3;270(5237):797–800.
Journal cover image

Published In

Science

DOI

ISSN

0036-8075

Publication Date

November 3, 1995

Volume

270

Issue

5237

Start / End Page

797 / 800

Location

United States

Related Subject Headings

  • X Chromosome
  • Trans-Activators
  • T-Lymphocytes
  • Signal Transduction
  • Severe Combined Immunodeficiency
  • STAT6 Transcription Factor
  • Receptors, Interleukin
  • RNA, Messenger
  • Protein-Tyrosine Kinases
  • Point Mutation