Postnatal tissue-specific disruption of transcription factor FoxN1 triggers acute thymic atrophy

Lili Cheng, Jianfei Guo, Liguang Sun, Jian Fu, Peter F. Barnes, Daniel Metzger, Pierre Chambon, Robert G. Oshima, Takashi Amagai, Dong Ming Su

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


The transcription factor FoxN1 is essential for differentiation of thymic epithelial cell (TEC) progenitors during thymic organogenesis. However, limited information is available on the postnatal contribution of FoxN1 to thymic maintenance. To address this question, we generated a loxP-floxed FoxN1 (fx) mouse with three different promoter-driven inducible CreERT transgenes. Postnatal ubiquitous deletion of FoxN1 caused dramatic thymic atrophy in 5 days and more severe deterioration in medullary TECs (mTECs) than in cortical TECs (cTECs). Induction of FoxN1 deletion selectively in K5 promoter-driven somatic epithelial cells (mostly mTECs and possibly some adult epithelial stem cells) was sufficient to cause significant thymic atrophy, whereas FoxN1 deletion in K18 promoter-driven somatic epithelial cells (mostly cTECs) was not. Thymic atrophy resulted from increased apoptosis and was associated with activation of the p53 gene in mature mTECs. Although FoxN1 is required for the development of both mTECs and cTECs in thymic organogenesis, it is most important for the maintenance of mTECs in the postnatal thymus, which are in turn necessary to prevent thymic atrophy.

Original languageEnglish
Pages (from-to)5836-5847
Number of pages12
JournalJournal of Biological Chemistry
Issue number8
StatePublished - Feb 19 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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