Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology.
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.
Matsumoto
Mitsuru
M
Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan. mitsuru@ier.tokushima-u.ac.jp
Zhou
Yiqing
Y
Matsuo
Shinji
S
Nakanishi
Hideki
H
Hirose
Kenji
K
Oura
Hajimu
H
Arase
Seiji
S
Ishida-Yamamoto
Akemi
A
Bando
Yoshimi
Y
Izumi
Keisuke
K
Kiyonari
Hiroshi
H
Oshima
Naoko
N
Nakayama
Rika
R
Matsushima
Akemi
A
Hirota
Fumiko
F
Mouri
Yasuhiro
Y
Kuroda
Noriyuki
N
Sano
Shigetoshi
S
Chaplin
David D
DD
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
D006023:Glycoproteins; C529128:corneodesmosin protein, mouse