title: Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology.
abstract: 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.
authors.affiliation: Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan. mitsuru@ier.tokushima-u.ac.jp
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuo
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirose
authors.forename: Hajimu
authors.initials: H
authors.lastname: Oura
authors.forename: Seiji
authors.initials: S
authors.lastname: Arase
authors.forename: Akemi
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Bando
authors.forename: Keisuke
authors.initials: K
authors.lastname: Izumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.forename: Naoko
authors.initials: N
authors.lastname: Oshima
authors.forename: Rika
authors.initials: R
authors.lastname: Nakayama
authors.forename: Akemi
authors.initials: A
authors.lastname: Matsushima
authors.forename: Fumiko
authors.initials: F
authors.lastname: Hirota
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Mouri
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kuroda
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Sano
authors.forename: David D
authors.initials: DD
authors.lastname: Chaplin
mesh_terms: D000818:Animals; D003896:Desmosomes / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D018390:Gene Targeting; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics*; D006197:Hair / Q000254:growth & development / Q000502:physiology*; D051379:Mice; D010641:Phenotype; D011565:Psoriasis / Q000473:pathology; D012868:Skin Abnormalities / Q000235:genetics / Q000648:ultrastructure; D012879:Skin Physiological Phenomena / Q000235:genetics*; D016038:Skin Transplantation
chemical_list: D006023:Glycoproteins; C529128:corneodesmosin protein, mouse