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Inborn mutation of <jats:italic>FoxN1<\/jats:italic> 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 <jats:italic>Rosa26<\/jats:italic>-<jats:italic>STOP<\/jats:italic><jats:sup>flox<\/jats:sup>\u2013<jats:italic>FoxN1<\/jats:italic> mice, in which over- and ectopic-expression of FoxN1 can be induced by various promoter-driven Cre-mediated deletions of the roadblock <jats:italic>STOP<\/jats:italic><jats:sup>flox<\/jats:sup> 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 <jats:italic>STOP<\/jats:italic><jats:sup>flox<\/jats:sup> mediated by progressive uCreER<jats:sup>T<\/jats:sup> 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<jats:sup>T<\/jats:sup>-mediated FoxN1 overexpression mice had a normal lifespan, induction of K5CreER<jats:sup>T<\/jats:sup> 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.<\/jats:p>","DOI":"10.1038\/cddis.2014.432","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T13:03:45Z","timestamp":1412859825000},"page":"e1457-e1457","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice"],"prefix":"10.1038","volume":"5","author":[{"given":"L","family":"Ruan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Mu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Burnley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Coder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Q","family":"Zhuge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D-M","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,10,9]]},"reference":[{"key":"BFcddis2014432_CR1","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.7150\/ijbs.5033","volume":"8","author":"Z Zhang","year":"2012","unstructured":"Zhang Z, Burnley P, Coder B, Su DM . 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