Biological Significance of FoxN1 Gain-of-Function Mutations During T and B Lymphopoiesis in Juvenile Mice

    October 2014 in “ Cell death and disease ”
    Linhui Ruan, Z. Zhang, Lili Mu, Preston Burnley, LONG WANG, Brandon Coder, Qǐ Chuan Zhuge, D-M Su
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    TLDR FoxN1 overexpression in young mice harms immune cell and skin development.
    The study investigated the effects of over- and ectopic-expression of FoxN1 in juvenile mice using Rosa26 - STOP flox – FoxN1 mice. It was found that K14Cre-mediated inborn FoxN1 overexpression caused neonatal lethality, skin permeability issues, and abnormal nursing. Ubiquitous deletion of the STOP flox in juvenile mice led to thymus and bone marrow abnormalities, increased medullary/cortical TEC ratios, and reduced T and B lymphopoiesis. K5CreER T-mediated FoxN1 overexpression in juveniles resulted in normal lifespan but negatively impacted thymocyte development and caused ichthyosis-like skin. The study concluded that FoxN1's activity is both temporal and tissue-specific, with its over- and ectopic-expression in early life adversely affecting TEC, T and B cell, and skin epithelial development.
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