Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic architecture and thymocyte survival.
This study describes abnormalities of the thymus in mice in which the Stat3 gene has been specifically disrupted behind the keratin 5 promoter. In these mice, virtually all of the thymic epithelial cells (TEC) were deficient for Stat3 activation. Adult mutant mice developed severe thymic hypoplasia, which included alterations in the cortical TEC architecture that coincided with the loss of thymocytes. Even during the asymptomatic period of preadolescence, these mice exhibited a higher susceptibility of the thymus to suboptimal doses of dexamethasone or gamma-irradiation, while their thymocytes per se were no more sensitive than controls. These results indicate that Stat3 in TEC plays an essential role in maintaining thymic architecture and thymocyte survival.
Sano
S
S
Department of Dermatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan. sano@derma.med.osaka-u.ac.jp
Takahama
Y
Y
Sugawara
T
T
Kosaka
H
H
Itami
S
S
Yoshikawa
K
K
Miyazaki
J
J
van Ewijk
W
W
Takeda
J
J
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology* / Q000528:radiation effects; D005720:Gamma Rays; D051379:Mice; D008817:Mice, Mutant Strains; D012038:Regeneration; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000473:pathology* / Q000528:radiation effects; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D003907:Dexamethasone