Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene.
Signal transducers and activators of transcription (Stats) are activated by tyrosine phosphorylation in response to cytokines, and are thought to mediate many of their functional responses. Stat6 is activated in response to interleukin (IL)-4 and may contribute to various functions including mitogenesis, T-helper cell differentiation and immunoglobulin isotype switching. To evaluate the role of Stat6, we generated Stat6-null mice (Stat6 -/-) by gene disruption in embryonic stem cells. The mice were viable, indicating the lack of a non-redundant function in normal development. Although naive lymphoid cell development was normal, Stat6 -/- mice were deficient in IL-4-mediated functions including Th2 helper T-cell differentiation, expression of cell surface markers, and immunoglobulin class switching to IgE. In contrast, IL-4-mediated proliferation was only partly affected.
Shimoda
K
K
Department of Biochemistry, St Jude Children's Research Hospital, Memphis, Tennessee 38105 USA.
van Deursen
J
J
Sangster
M Y
MY
Sarawar
S R
SR
Carson
R T
RT
Tripp
R A
RA
Chu
C
C
Quelle
F W
FW
Nosaka
T
T
Vignali
D A
DA
Doherty
P C
PC
Grosveld
G
G
Paul
W E
WE
Ihle
J N
JN
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D015342:DNA Probes; D018390:Gene Targeting; D007109:Immunity / Q000235:genetics / Q000502:physiology; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D015342:DNA Probes; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E