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Low threshold for cutaneous allergen sensitization but no spontaneous dermatitis or atopy in filaggrin-deficient mice.

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Pippel,  Martin
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Winkler,  Sylke
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Hiller,  Michael
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Muhandes, L., Chapsa, M., Pippel, M., Behrendt, R., Ge, Y., Dahl, A., et al. (2021). Low threshold for cutaneous allergen sensitization but no spontaneous dermatitis or atopy in filaggrin-deficient mice. The Journal of investigative dermatology, doi: 10.1016/j.jid.2021.02.763, pp. 1-1. doi:10.1016/j.jid.2021.02.763.


Cite as: https://hdl.handle.net/21.11116/0000-0008-DAD7-0
Abstract
Loss of filaggrin (FLG) causes Ichthyosis vulgaris. Reduced filaggrin expression compromises epidermal barrier function and is associated with atopic dermatitis, allergy and asthma. The flaky tail mouse harbors two mutations that affect the skin barrier, Flgft, resulting in hypomorphic FLG expression, and Tmem79matted inactivating transmembrane protein 79. Mice defective only for Tmem79 featured dermatitis and systemic atopy, but also Flgft/ft BALB/c congenic mice developed eczema, high IgE and spontaneous asthma, suggesting that Flg protects from atopy. In contrast, a targeted Flg knock out mutation backcrossed to BALB/c did not result in dermatits or atopy. To resolve this discrepancy, we generated Flg-deficient mice on pure BALB/c background by inactivating Flg in BALB/c embryos. These animals feature an ichthyosis phenotype, barrier defect and facilitated percutaneous sensitization. However, they do not develop dermatitis or atopy. Whole genome sequencing of the atopic Flgft BALB/c congenics revealed that they were homozygous for the atopy-causing Tmem79matted mutation. In summary, we show that Flg-deficiency does not cause atopy in mice, in line with lack of atopic disease in a fraction of Ichthyosis vulgaris patients carrying two FLG null alleles. However, absence of FLG likely promotes and modulates dermatitis caused by other genetic barrier defects.