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Foxc1 Ablated Mice Are Anhidrotic and Recapitulate Features of Human Miliaria Sweat Retention Disorder.
J Invest Dermatol. 2017 01; 137(1):38-45.JI

Abstract

Sweat glands are critical for thermoregulation. The single tubular structure of sweat glands has a lower secretory portion and an upper reabsorptive duct leading to the secretory pore in the skin. Genes that determine sweat gland structure and function are largely unidentified. Here we report that a Fox family transcription factor, Foxc1, is obligate for appreciable sweat duct activity in mice. When Foxc1 was specifically ablated in skin, sweat glands appeared mature, but the mice were severely hypohidrotic. Morphologic analysis revealed that sweat ducts were blocked by hyperkeratotic or parakeratotic plugs. Consequently, lumens in ducts and secretory portions were dilated, and blisters and papules formed on the skin surface in the knockout mice. The phenotype was strikingly similar to the human sweat retention disorder miliaria. We further show that Foxc1 deficiency ectopically induces the expression of keratinocyte terminal differentiation markers in the duct luminal cells, which most likely contribute to keratotic plug formation. Among those differentiation markers, we show that Sprr2a transcription is directly repressed by overexpressed Foxc1 in keratinocytes. In summary, Foxc1 regulates sweat duct luminal cell differentiation, and mutant mice mimic miliaria and provide a possible animal model for its study.

Authors+Show Affiliations

Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA. Electronic address: cuic@mail.nih.gov.Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

27592801

Citation

Cui, Chang-Yi, et al. "Foxc1 Ablated Mice Are Anhidrotic and Recapitulate Features of Human Miliaria Sweat Retention Disorder." The Journal of Investigative Dermatology, vol. 137, no. 1, 2017, pp. 38-45.
Cui CY, Ishii R, Campbell DP, et al. Foxc1 Ablated Mice Are Anhidrotic and Recapitulate Features of Human Miliaria Sweat Retention Disorder. J Invest Dermatol. 2017;137(1):38-45.
Cui, C. Y., Ishii, R., Campbell, D. P., Michel, M., Piao, Y., Kume, T., & Schlessinger, D. (2017). Foxc1 Ablated Mice Are Anhidrotic and Recapitulate Features of Human Miliaria Sweat Retention Disorder. The Journal of Investigative Dermatology, 137(1), 38-45. https://doi.org/10.1016/j.jid.2016.08.012
Cui CY, et al. Foxc1 Ablated Mice Are Anhidrotic and Recapitulate Features of Human Miliaria Sweat Retention Disorder. J Invest Dermatol. 2017;137(1):38-45. PubMed PMID: 27592801.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Foxc1 Ablated Mice Are Anhidrotic and Recapitulate Features of Human Miliaria Sweat Retention Disorder. AU - Cui,Chang-Yi, AU - Ishii,Ryuga, AU - Campbell,Dean P, AU - Michel,Marc, AU - Piao,Yulan, AU - Kume,Tsutomu, AU - Schlessinger,David, Y1 - 2016/09/01/ PY - 2016/02/01/received PY - 2016/08/16/revised PY - 2016/08/17/accepted PY - 2016/9/7/pubmed PY - 2017/7/20/medline PY - 2016/9/6/entrez SP - 38 EP - 45 JF - The Journal of investigative dermatology JO - J. Invest. Dermatol. VL - 137 IS - 1 N2 - Sweat glands are critical for thermoregulation. The single tubular structure of sweat glands has a lower secretory portion and an upper reabsorptive duct leading to the secretory pore in the skin. Genes that determine sweat gland structure and function are largely unidentified. Here we report that a Fox family transcription factor, Foxc1, is obligate for appreciable sweat duct activity in mice. When Foxc1 was specifically ablated in skin, sweat glands appeared mature, but the mice were severely hypohidrotic. Morphologic analysis revealed that sweat ducts were blocked by hyperkeratotic or parakeratotic plugs. Consequently, lumens in ducts and secretory portions were dilated, and blisters and papules formed on the skin surface in the knockout mice. The phenotype was strikingly similar to the human sweat retention disorder miliaria. We further show that Foxc1 deficiency ectopically induces the expression of keratinocyte terminal differentiation markers in the duct luminal cells, which most likely contribute to keratotic plug formation. Among those differentiation markers, we show that Sprr2a transcription is directly repressed by overexpressed Foxc1 in keratinocytes. In summary, Foxc1 regulates sweat duct luminal cell differentiation, and mutant mice mimic miliaria and provide a possible animal model for its study. SN - 1523-1747 UR - https://www.unboundmedicine.com/medline/citation/27592801/Foxc1_Ablated_Mice_Are_Anhidrotic_and_Recapitulate_Features_of_Human_Miliaria_Sweat_Retention_Disorder_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-202X(16)32345-4 DB - PRIME DP - Unbound Medicine ER -