title: Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice.
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-STOP(flox)-FoxN1 mice, in which over- and ectopic-expression of FoxN1 can be induced by various promoter-driven Cre-mediated deletions of the roadblock STOP(flox) 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 STOP(flox) mediated by progressive uCreER(T) 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 K5CreER(T)-mediated FoxN1 overexpression mice had a normal lifespan, induction of K5CreER(T) 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.
authors.affiliation: 1] Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China [2] Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Ruan
authors.affiliation: Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Mu
authors.affiliation: Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Burnley
authors.affiliation: Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
authors.forename: B
authors.initials: B
authors.lastname: Coder
authors.affiliation: Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhuge
authors.affiliation: 1] Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China [2] Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
authors.forename: D-M
authors.initials: DM
authors.lastname: Su
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001853:Bone Marrow / Q000254:growth & development / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D038041:Lymphopoiesis; D051379:Mice / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009154:Mutation; D009928:Organ Specificity; D012867:Skin / Q000254:growth & development / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000254:growth & development / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C090140:Whn protein