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Developmental defects of lymphoid cells in Jak3 kinase-deficient mice.

Jak3 is a tyrosine kinase mediating cytokine receptor signaling through the association with the common gamma chain of the cytokine receptors such as IL-2, IL-4, IL-7, IL-9, and IL-15. Unlike other members of the Jak family, the expression of Jak3 is highly restricted in hematopoietic cells. To elucidate in vivo function of Jak3, Jak3-deficient mice were generated by homologous recombination. Mice homozygous for Jak3 null mutation showed severe defects, specifically in lymphoid cells. B cell precursors in bone marrow, thymocytes, and both T and B cells in the spleen drastically decreased, although these defects were significantly recovered as aging occurred. Peripheral lymph nodes, NK cells, dendritic epidermal T cells, and intestinal intraepithelial gamma delta T cells were absent. Normal number of hematopoietic stem cells in bone marrow from Jak3-deficient mice and the similar capability to generate myeloid and erythroid colonies as wild-type mice indicated specific defects in lymphoid stem cells. Furthermore, the abnormal architecture of lymphoid organs suggested the involvement of Jak3 in the function of epithelial cells. T cells developed in the mutant mice did not respond to either IL-2, IL-4, or IL-7. These findings establish the crucial role of Jak3 in the development of lymphoid cells.

Pubmed ID: 8777722

Authors

  • Park SY
  • Saijo K
  • Takahashi T
  • Osawa M
  • Arase H
  • Hirayama N
  • Miyake K
  • Nakauchi H
  • Shirasawa T
  • Saito T

Journal

Immunity

Publication Data

December 16, 1995

Associated Grants

None

Mesh Terms

  • Animals
  • Animals, Newborn
  • Base Sequence
  • Cell Differentiation
  • Hematopoietic Stem Cells
  • Immunophenotyping
  • Janus Kinase 3
  • Lymphoid Tissue
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Protein-Tyrosine Kinases