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Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein.

Koch PJ, de Viragh PA, Scharer E, Bundman D, Longley MA, Bickenbach J, Kawachi Y, Suga Y, Zhou Z, Huber M, Hohl D, Kartasova T, Jarnik M, Steven AC, Roop DR - J. Cell Biol. (2000)

Bottom Line: The epidermal cornified cell envelope (CE) is a complex protein-lipid composite that replaces the plasma membrane of terminally differentiated keratinocytes.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

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.

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The stratum corneum of Lor−/− mice shows increased susceptibility to mechanical stress. The back skin of newborn Lor−/− (Null) and wild-type pups was tape stripped ten times. Animals were killed and the number of stratum corneum cell layers was determined by electron microscopy. Open bars (untreated skin); closed bars (tape stripped skin). Note that mutant mice lost approximately three times more cell layers.
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Figure 6: The stratum corneum of Lor−/− mice shows increased susceptibility to mechanical stress. The back skin of newborn Lor−/− (Null) and wild-type pups was tape stripped ten times. Animals were killed and the number of stratum corneum cell layers was determined by electron microscopy. Open bars (untreated skin); closed bars (tape stripped skin). Note that mutant mice lost approximately three times more cell layers.

Mentions: To determine whether the abnormal CE affected the biomechanical properties of the mutant epidermis, we performed tape stripping experiments and determined the loss of cell layers from the stratum corneum by electron microscopy. As summarized in Fig. 6, the stratum corneum of Lor−/− backskin was less resistant to mechanical stress than wild-type control tissue. Mutant mice lost approximately three times more cell layers than control mice. Nevertheless, the fact that tissues that are naturally exposed to mechanical stress (paws, legs, and axilla) do not show gross or microscopic lesions, suggests that the mechanical stability of Lor−/− epidermis is not significantly impaired.


Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein.

Koch PJ, de Viragh PA, Scharer E, Bundman D, Longley MA, Bickenbach J, Kawachi Y, Suga Y, Zhou Z, Huber M, Hohl D, Kartasova T, Jarnik M, Steven AC, Roop DR - J. Cell Biol. (2000)

The stratum corneum of Lor−/− mice shows increased susceptibility to mechanical stress. The back skin of newborn Lor−/− (Null) and wild-type pups was tape stripped ten times. Animals were killed and the number of stratum corneum cell layers was determined by electron microscopy. Open bars (untreated skin); closed bars (tape stripped skin). Note that mutant mice lost approximately three times more cell layers.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192642&req=5

Figure 6: The stratum corneum of Lor−/− mice shows increased susceptibility to mechanical stress. The back skin of newborn Lor−/− (Null) and wild-type pups was tape stripped ten times. Animals were killed and the number of stratum corneum cell layers was determined by electron microscopy. Open bars (untreated skin); closed bars (tape stripped skin). Note that mutant mice lost approximately three times more cell layers.
Mentions: To determine whether the abnormal CE affected the biomechanical properties of the mutant epidermis, we performed tape stripping experiments and determined the loss of cell layers from the stratum corneum by electron microscopy. As summarized in Fig. 6, the stratum corneum of Lor−/− backskin was less resistant to mechanical stress than wild-type control tissue. Mutant mice lost approximately three times more cell layers than control mice. Nevertheless, the fact that tissues that are naturally exposed to mechanical stress (paws, legs, and axilla) do not show gross or microscopic lesions, suggests that the mechanical stability of Lor−/− epidermis is not significantly impaired.

Bottom Line: The epidermal cornified cell envelope (CE) is a complex protein-lipid composite that replaces the plasma membrane of terminally differentiated keratinocytes.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

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.

Show MeSH
Related in: MedlinePlus