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

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 lymphopoies...

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Main Authors:	Ruan, L, Zhang, Z, Mu, L, Burnley, P, Wang, L, Coder, B, Zhuge, Q, Su, D-M
Format:	Online
Language:	English
Published:	Nature Publishing Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237256/

id	pubmed-4237256
recordtype	oai_dc
spelling	pubmed-42372562014-11-26 Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice Ruan, L Zhang, Z Mu, L Burnley, P Wang, L Coder, B Zhuge, Q Su, D-M Original Article 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 K5CreERT-mediated 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. Over- and ectopic-expression of FoxN1 in early life adversely influence immature TEC, T and B cell, and skin epithelial development. Nature Publishing Group 2014-10 2014-10-09 /pmc/articles/PMC4237256/ /pubmed/25299782 http://dx.doi.org/10.1038/cddis.2014.432 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ruan, L Zhang, Z Mu, L Burnley, P Wang, L Coder, B Zhuge, Q Su, D-M
spellingShingle	Ruan, L Zhang, Z Mu, L Burnley, P Wang, L Coder, B Zhuge, Q Su, D-M Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice
author_facet	Ruan, L Zhang, Z Mu, L Burnley, P Wang, L Coder, B Zhuge, Q Su, D-M
author_sort	Ruan, L
title	Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice
title_short	Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice
title_full	Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice
title_fullStr	Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice
title_full_unstemmed	Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice
title_sort	biological significance of foxn1 gain-of-function mutations during t and b lymphopoiesis in juvenile mice
description	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 K5CreERT-mediated 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. Over- and ectopic-expression of FoxN1 in early life adversely influence immature TEC, T and B cell, and skin epithelial development.
publisher	Nature Publishing Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237256/
_version_	1613158622826594304

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

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