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Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 932-939
Dysregulated Myelopoiesis in Mice Lacking Jak3
William J. Grossman,
James W. Verbsky,
Liping Yang,
Leslie J. Berg,
Larry E. Fields,
David D. Chaplin, and
Lee Ratner
From the Divisions of Molecular Microbiology and Cardiology, the
Departments of Pathology and Medicine, Washington University School of
Medicine, St Louis, MO; Howard Hughes Medical Institute, Washington
University School of Medicine, St Louis, MO; and the Department
of Molecular and Cellular Biology, Harvard University, Cambridge,
MA.
Jak3 is a cytoplasmic tyrosine kinase that associates with the
common chain of the interleukin-2 (IL-2) receptor and is involved in
the function of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15.
Mice deficient in Jak3 have few T and B cells, and no natural killer
cells. Herein we show that the myeloid lineages in these mice are also
affected by the loss of Jak3. Mice lacking Jak3 exhibit splenomegaly by
4 months of age. Peripheral blood smears show an increase in the number
of neutrophils and cells of the monocytic lineage. Flow cytometry of
splenocytes and peripheral blood show a significant increase in
Fc RII/III(FcR)/Mac-1, FcR/Gr-1, and FcR/F4/80
double-positive cells in  / and +/ mice compared to wild-type
mice, consistent with an expansion of cells of the myeloid lineages. In
addition, as the mice age, F4/80 and CD3 positive mononuclear cells
infiltrate the kidneys, lungs, and liver of these mice. When
Jak3/ mice are crossed with a transgenic mouse expressing Jak3 in
the T and NK cell compartments, the splenomegaly and myeloid expansion
are accentuated. These data correlate with the constitutive activation
of T cells in the periphery as the transgenic cells lose their
expression of Jak3 with age. However, when Jak3/ mice are crossed
with RAG-1-deficient animals, no splenomegaly or myeloid expansion is
apparent. These results indicate that the loss of Jak3 in the T-cell
compartment drives the expansion of the myeloid lineages.
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