A tale of two STAT6 knock out mice in the induction of experimental autoimmune encephalomyelitis.
T helper 2 (Th2) cytokines are known to be important in protection against experimental autoimmune encephalomyelitis (EAE). To investigate the role of the signal transducer and activator of transcription factor 6 (STAT6) in EAE we used mice with two different targeted disruptions of the STAT6 gene. In this report, we show that mice with a targeted deletion of the first coding exon of the SH2 domain of STAT6 induce Th2 cell differentiation and are resistant to EAE induction. By contrast, STAT6(-/-) mice generated by deletion of amino acids 505 to 584 encoding the SH2 domain of STAT6 are defective in Th2 cell differentiation and develop very severe EAE. These results suggest that an altered STAT6 gene can be more efficient than wild type STAT6 in regulating the autoimmune response in EAE.
Wang
Yongmei
Y
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Evans
J T
JT
Rodriguez
Frederick
F
Fields
Patrick
P
Mueller
Cynthia
C
Chitnis
Tanuja
T
Khoury
Samia J
SJ
Bynoe
Margaret S
MS
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay; D017353:Gene Deletion; D015870:Gene Expression / Q000235:genetics; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050800:STAT6 Transcription Factor / Q000172:deficiency* / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000502:physiology; D018909:src Homology Domains / Q000235:genetics*
D016207:Cytokines; D008565:Membrane Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse