Truncated pStat5B is associated with the Idd4 locus in NOD mice.
We investigate JAK-STAT5 activation and its relationship to full-length Stat5B (FL-Stat5) and constitutive phosphorylated carboxy-truncated Stat5B (ct-pStat5) in four different strains of mouse. Our electrophoresis mobility shift assays data indicate constitutive phosphorylation of full-length-Stat5 (p<0.001) and DNA binding in NOD but not in B6 mice. Our data suggest that the relative ratio of FL-Stat5: ct-Stat5 in NOD is 5- to 8-fold lower (p<0.0001) when compared with normal B6 mice. Additionally, EMSAs data from B6.NOD/c11 suggest contribution of Idd4 susceptibility locus on chromosome 11 in constitutive phosphorylation of Stat5 in NOD mice. The presence of ct-pStat5 in regulatory T cells of NOD mice suggests this form of Stat5 is associated with impaired function of Tregs in NOD mouse. In agreement with our previous report the JAK-Stat5B defective pathway in NOD mice along with other defective factors is associated with the pathogenesis of autoimmune type 1 diabetes in NOD mice.
Davoodi-Semiromi
Abdoreza
A
Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA. semiromi@pathology.ufl.edu
McDuffie
Marcia
M
Litherland
Sally
S
Clare-Salzler
Michael
M
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D010446:Peptide Fragments; D050799:STAT5 Transcription Factor; C494096:Stat5b protein, mouse