Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice

L. Ruan, Z. Zhang, L. Mu, P. Burnley, L. Wang, B. Coder, Q. Zhuge, D. M. Su

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

FoxN1 is cell-autonomously expressed in skin and thymic epithelial cells (TECs), essential for their development. Inborn mutation of FoxN1 results in hair follicle and TEC development failure, whereas insufficient postnatal FoxN1 expression induces thymic atrophy, resulting in declined T lymphopoiesis. Although upregulating FoxN1 expression in the aged FoxN1-declined thymus rejuvenates T lymphopoiesis, whether its over- and ectopic-expression in early life is beneficial for T lymphopoiesis is unknown. Using our newly generated Rosa26-STOPflox-FoxN1 mice, in which over- and ectopic-expression of FoxN1 can be induced by various promoter-driven Cre-mediated deletions of the roadblock STOPflox in early life, we found that K14Cre-mediated inborn FoxN1 overexpression induced neonatal lethality, exhibited abnormal permeability in the skin and abnormal nursing. Ubiquitous deletion of the STOPflox mediated by progressive uCreERT leakage in juvenile mice affected thymus and bone marrow normality, resulting in an increased ratio of medullary/cortical TECs, along with declined T and B lymphopoiesis. Although the K5CreERTmediated FoxN1 overexpression mice had a normal lifespan, induction of K5CreERT activation in juveniles adversely influenced= total thymoycte development and produced ichthyosis-like skin. Therefore, FoxN1 has temporal and tissue-specific activity. Overand ectopic-expression of FoxN1 in early life adversely influence immature TEC, T and B cell, and skin epithelial development.

Original languageEnglish
Article numbere1457
JournalCell Death and Disease
Volume5
Issue number10
DOIs
StatePublished - 1 Jan 2014

Fingerprint Dive into the research topics of 'Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice'. Together they form a unique fingerprint.

  • Cite this