Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses.
Herein we report the generation of mice lacking the ubiquitously expressed Janus kinase, Jak1. Jak1-/- mice are runted at birth, fail to nurse, and die perinatally. Although Jak1-/- cells are responsive to many cytokines, they fail to manifest biologic responses to cytokines that bind to three distinct families of cytokine receptors. These include all class II cytokine receptors, cytokine receptors that utilize the gamma(c) subunit for signaling, and the family of cytokine receptors that depend on the gp130 subunit for signaling. Our results thus demonstrate that Jak1 plays an essential and nonredundant role in promoting biologic responses induced by a select subset of cytokine receptors, including those in which Jak utilization was thought to be nonspecific.
Rodig
S J
SJ
Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Meraz
M A
MA
White
J M
JM
Lampe
P A
PA
Riley
J K
JK
Arthur
C D
CD
King
K L
KL
Sheehan
K C
KC
Yin
L
L
Pennica
D
D
Johnson
E M
EM
Schreiber
R D
RD
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001724:Birth Weight; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D053613:Janus Kinase 1; D019891:Leukopoiesis; D008024:Ligands; D008264:Macrophages / Q000166:cytology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology; D009475:Neurons, Afferent / Q000166:cytology; D009929:Organ Size; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D018121:Receptors, Cytokine / Q000502:physiology*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D016207:Cytokines; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; C494200:Il6st protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1