Dysregulated myelopoiesis in mice lacking Jak3. Blood 1999 Aug 01;94(3):932-9
Date
07/27/1999Pubmed ID
10419884DOI
10.1182/blood.v94.3.932.415k30_932_939Scopus ID
2-s2.0-0033179324 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
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 FcgammaRII/III(FcgammaR)/Mac-1, FcgammaR/Gr-1, and FcgammaR/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.
Author List
Grossman WJ, Verbsky JW, Yang L, Berg LJ, Fields LE, Chaplin DD, Ratner LAuthor
James Verbsky MD, PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsFlow Cytometry
Gene Deletion
Homeodomain Proteins
Immunohistochemistry
Janus Kinase 3
Leukopoiesis
Mice
Mice, Knockout
Protein-Tyrosine Kinases
Receptors, IgG
Receptors, Interleukin-2