DEVELOPMENTAL DEFECTS OF LYMPHOID-CELLS IN JAK3 KINASE-DEFICIENT MICE

Jak3 is a tyrosine kinase mediating cytokine receptor signaling throug h the association with the common gamma chain of the cytokine receptor s such as IL-2, IL-4, IL-7, IL-9, and IL-15. Unlike other members of t he Jak family, the expression of Jak3 is highly restricted in hematopo ietic cells. To elucidate in vivo function of Jak3, Jak3-deficient mic e 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 i n the spleen drastically decreased, although these defects were signif icantly recovered as aging occurred. Peripheral lymph nodes, NK cells, dendritic epidermal T cells, and intestinal intraepithelial gamma del ta T cells were absent. Normal number of hematopoietic stem cells in b one marrow from Jak3-deficient mice and the similar capability to gene rate myeloid and erythroid colonies as wild-type mice indicated specif ic defects in lymphoid stem cells. Furthermore, the abnormal architect ure of lymphoid organs suggested the involvement of Jak3 in the functi on of epithelial cells. T cells developed in the mutant mice did not r espond to either IL-2, IL-4, or IL-7. These findings establish the cru cial role of Jak3 in the development of lymphoid cells.