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.
Park
S Y
SY
Division of Molecular Genetics, Chiba University School of Medicine, Japan.
Saijo
K
K
Takahashi
T
T
Osawa
M
M
Arase
H
H
Hirayama
N
N
Miyake
K
K
Nakauchi
H
H
Shirasawa
T
T
Saito
T
T
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002454:Cell Differentiation; D006412:Hematopoietic Stem Cells / Q000473:pathology; D016130:Immunophenotyping; D053616:Janus Kinase 3; D008221:Lymphoid Tissue / Q000201:enzymology / Q000254:growth & development / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000172:deficiency*
D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3