TY - JOUR
T1 - Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses
AU - Rodig, Scott J.
AU - Meraz, Marco A.
AU - White, J. Michael
AU - Lampe, Pat A.
AU - Riley, Joan K.
AU - Arthur, Cora D.
AU - King, Kathleen L.
AU - Sheehan, Kathleen C.F.
AU - Yin, Li
AU - Pennica, Diane
AU - Johnson, Eugene M.
AU - Schreiber, Robert D.
N1 - Funding Information:
We are grateful to Michel Aguet (ISREC, Lausanne, Switzerland) for helpful discussions, William Snider and Jeffrey Elliot (Department of Neurology and Neurological Surgery, Washington University School of Medicine) for conducting the in situ hybridization studies for LIFRβ expression, and Jeffrey Saffitz (Department of Pathology, Washington University School of Medicine) for pathology studies on the Jak1 −/− mice. We also thank Paul Allen, Kenneth Murphy, Andrey Shaw, and Emil Unanue (Department of Pathology, Washington University School of Medicine) for helpful suggestions. The studies conducted in the R. D. S. laboratory were supported by National Institutes of Health grant CA43059 and grants from Genentech, Inc. and Abbott Laboratories. Studies conducted in the E. M. J. laboratory were supported by National Institutes of Health grant AG12947.
PY - 1998/5/1
Y1 - 1998/5/1
N2 - Herein we report the generation of mice lacking the ubiquitously expressed Janus kinase, Jak1. Jak1-1mice are runted at birth, fall to nurse, and die perinatally. Although Jak1-/- cells are responsive to many cytokines, they fall 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 γ(o) 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.
AB - Herein we report the generation of mice lacking the ubiquitously expressed Janus kinase, Jak1. Jak1-1mice are runted at birth, fall to nurse, and die perinatally. Although Jak1-/- cells are responsive to many cytokines, they fall 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 γ(o) 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.
UR - http://www.scopus.com/inward/record.url?scp=0032076183&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)81166-6
DO - 10.1016/S0092-8674(00)81166-6
M3 - Article
C2 - 9590172
AN - SCOPUS:0032076183
SN - 0092-8674
VL - 93
SP - 373
EP - 383
JO - Cell
JF - Cell
IS - 3
ER -