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© The Rockefeller University Press,
0021-9525/2000//389 $5.00
The Journal of Cell Biology, Volume 151, Number 2,
, 2000 389-400
Original Article |
Lessons from Loricrin-Deficient Mice
: Compensatory Mechanisms Maintaining Skin Barrier Function in the Absence of a Major Cornified Envelope Protein
b Department of Dermatology, Baylor College of Medicine, Houston, Texas 77030
c Department of Dermatology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
d Laboratory of Cutaneous Biology, Department of Dermatology, University of Lausanne 1011, Lausanne, Switzerland
e Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Disease, Bethesda, Maryland 20892
f Laboratory of Structural Biology, National Institute of Arthritis and Musculoskeletal and Skin Disease, Bethesda, Maryland 20892
Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.(713) 798-3800(713) 798-4966
The epidermal cornified cell envelope (CE) is a complex protein–lipid composite that replaces the plasma membrane of terminally differentiated keratinocytes. This lamellar structure is essential for the barrier function of the skin and has the ability to prevent the loss of water and ions and to protect from environmental hazards. The major protein of the epidermal CE is loricrin, contributing
70% by mass. We have generated mice that are deficient for this protein. These mice showed a delay in the formation of the skin barrier in embryonic development. At birth, homozygous mutant mice weighed less than control littermates and showed skin abnormalities, such as congenital erythroderma with a shiny, translucent skin. Tape stripping experiments suggested that the stratum corneum stability was reduced in newborn Lor–/– mice compared with wild-type controls. Isolated mutant CEs were more easily fragmented by sonication in vitro, indicating a greater susceptibility to mechanical stress. Nevertheless, we did not detect impaired epidermal barrier function in these mice. Surprisingly, the skin phenotype disappeared 4–5 d after birth. At least one of the compensatory mechanisms preventing a more severe skin phenotype in newborn Lor–/– mice is an increase in the expression of other CE components, such as SPRRP2D and SPRRP2H, members of the family of "small proline rich proteins", and repetin, a member of the "fused gene" subgroup of the S100 gene family.
Key Words: loricrin • knockout mice • cornified envelope • small proline-rich protein • repetin
© 2000 The Rockefeller University Press
J. Bickenbach's present address is Department of Anatomy & Cell Biology, University of Iowa, Iowa City, IA 52242.Y. Suga's present address is Department of Dermatology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
M. Jarnik's present address is Fox Chase Cancer Center, Philadelphia, PA 19111.
Abbreviations used in this paper: CE, cornified cell envelope; E, embryonic day; ES, embryonic stem; HSV-tk, herpes simplex virus type 1 thymidine-kinase minigene; RPA, RNase protection assay; SPRRP, small proline-rich protein; TEWL, transepidermal water loss; TGase, transglutaminase; VS, Vohwinkel's syndrome.
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