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BIOLOGICAL SCIENCES / MEDICAL SCIENCES
Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology

Mitsuru Matsumoto^a,b, Yiqing Zhou^c, Shinji Matsuo^d, Hideki Nakanishi^d, Kenji Hirose^e, Hajimu Oura^e, Seiji Arase^e, Akemi Ishida-Yamamoto^f, Yoshimi Bando^g, Keisuke Izumi^g, Hiroshi Kiyonari^h, Naoko Oshima^h, Rika Nakayama^h, Akemi Matsushima^a, Fumiko Hirota^a, Yasuhiro Mouri^a, Noriyuki Kuroda^a, Shigetoshi Sanoⁱ, and David D. Chaplin^j

^aDivision of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan; ^cKortex Laboratories, Orange Village, OH 44022-1412; ^dSection of Plastic and Reconstructive Surgery, University Hospital, University of Tokushima, Tokushima 770-8503, Japan; ^eDepartment of Dermatology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8503, Japan; ^fDepartment of Dermatology, Asahikawa Medical College, Asahikawa 078-8510, Japan; ^gDepartment of Molecular and Environmental Pathology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8503, Japan; ^hLaboratory for Animal Resources and Genetic Engineering, Center for Developmental Biology, RIKEN Kobe, Kobe 650-0047, Japan; ⁱDepartment of Dermatology, Kochi University School of Medicine, Nankoku 783-8505, Japan; and ^jDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294-2170

Edited by Kathryn V. Anderson, Sloan–Kettering Institute, New York, NY, and approved February 29, 2008 (received for review October 1, 2007)

Controlled proteolytic degradation of specialized junctional structures, corneodesmosomes, by epidermal proteases is an essential process for physiological desquamation of the skin. Corneodesmosin (CDSN) is an extracellular component of corneodesmosomes and, although considerable debate still exists, genetic studies have suggested that the CDSN gene in the major psoriasis-susceptibility locus (PSORS1) may be responsible for susceptibility to psoriasis, a human skin disorder characterized by excessive growth and aberrant differentiation of keratinocytes. CDSN is also expressed in the inner root sheath of hair follicles, and a heterozygous nonsense mutation of the CDSN gene in humans is associated with scalp-specific hair loss of poorly defined etiology. Here, we have investigated the pathogenetic roles of CDSN loss of function in the development of skin diseases by generating a mouse strain with targeted deletion of the Cdsn gene. Cdsn-deficient mouse skin showed detachment of the stratum corneum from the underlying granular layer and/or detachment within the upper granular layers due to the disrupted integrity of the corneodesmosomes. When grafted onto immunodeficient mice, Cdsn-deficient skin showed rapid hair loss together with epidermal abnormalities resembling psoriasis. These results underscore the essential roles of CDSN in hair physiology and suggest functional relevance of CDSN gene polymorphisms to psoriasis susceptibility.

corneodesmosome | hypotrichosis simplex of the scalp | keratinocyte | psoriasis

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0709345105/DCSupplemental.

^bTo whom correspondence should be addressed. E-mail: mitsuru{at}ier.tokushima-u.ac.jp

© 2008 by The National Academy of Sciences of the USA

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