title: Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein.
abstract: 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 approximately 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.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Koch
authors.forename: P A
authors.initials: PA
authors.lastname: de Viragh
authors.forename: E
authors.initials: E
authors.lastname: Scharer
authors.forename: D
authors.initials: D
authors.lastname: Bundman
authors.forename: M A
authors.initials: MA
authors.lastname: Longley
authors.forename: J
authors.initials: J
authors.lastname: Bickenbach
authors.forename: Y
authors.initials: Y
authors.lastname: Kawachi
authors.forename: Y
authors.initials: Y
authors.lastname: Suga
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.forename: M
authors.initials: M
authors.lastname: Huber
authors.forename: D
authors.initials: D
authors.lastname: Hohl
authors.forename: T
authors.initials: T
authors.lastname: Kartasova
authors.forename: M
authors.initials: M
authors.lastname: Jarnik
authors.forename: A C
authors.initials: AC
authors.lastname: Steven
authors.forename: D R
authors.initials: DR
authors.lastname: Roop
mesh_terms: D000220:Adaptation, Biological; D000595:Amino Acid Sequence; D000818:Animals; D001696:Biomechanical Phenomena; D002462:Cell Membrane; D003001:Cloning, Molecular; D055233:Cornified Envelope Proline-Rich Proteins; D004817:Epidermis / Q000502:physiology*; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010539:Permeability; D009418:S100 Proteins / Q000096:biosynthesis; D012879:Skin Physiological Phenomena / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; C108628:Rptn protein, mouse; D009418:S100 Proteins; C491983:Sprr2d protein, mouse; C491980:Sprr2h protein, mouse; C064554:loricrin