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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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Increased repetin expression in Lor−/− mice. (A) Staining of back skin from a newborn wild-type mouse with antibodies against repetin (green) and K14 (red). Overlapping expression of both proteins results in yellow fluorescence. Note the focal expression pattern and lack of accumulation in the stratum corneum. (B) Staining of Lor−/− neonatal back skin. Note the more uniform expression pattern and the presence of repetin at the periphery of corneocytes in the stratum corneum. Also, note the apparent accumulation of repetin in granules in the granular layer of both wild-type and Lor−/− epidermis.
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Figure 8: Increased repetin expression in Lor−/− mice. (A) Staining of back skin from a newborn wild-type mouse with antibodies against repetin (green) and K14 (red). Overlapping expression of both proteins results in yellow fluorescence. Note the focal expression pattern and lack of accumulation in the stratum corneum. (B) Staining of Lor−/− neonatal back skin. Note the more uniform expression pattern and the presence of repetin at the periphery of corneocytes in the stratum corneum. Also, note the apparent accumulation of repetin in granules in the granular layer of both wild-type and Lor−/− epidermis.

Mentions: We also examined the expression of repetin by RPA. Repetin is a relatively new member of the “fused gene” S100 subgroup consisting of profilaggrin, trichohyalin, and repetin (Krieg et al. 1997). Repetin also shares homology with CE components and was recently shown to be upregulated along with SPRRP2A in another knockout mouse exhibiting a barrier defect (Segre et al. 1999). Repetin transcripts were increased approximately threefold at E17.5, twofold in newborns, and fourfold in 4-d-old Lor−/− back skin when compared with controls (Fig. 7 B). We were also able to demonstrate an increase in repetin in Lor−/− epidermis at the protein level by immunofluorescence microscopy. In wild-type epidermis, repetin is expressed focally, and it appears to be localized in granules. There is no obvious accumulation in the stratum corneum (Fig. 8 A). However, in Lor−/− epidermis, repetin is expressed more uniformily, and it appears to localize at the periphery of CE in the stratum corneum (Fig. 8 B).


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)

Increased repetin expression in Lor−/− mice. (A) Staining of back skin from a newborn wild-type mouse with antibodies against repetin (green) and K14 (red). Overlapping expression of both proteins results in yellow fluorescence. Note the focal expression pattern and lack of accumulation in the stratum corneum. (B) Staining of Lor−/− neonatal back skin. Note the more uniform expression pattern and the presence of repetin at the periphery of corneocytes in the stratum corneum. Also, note the apparent accumulation of repetin in granules in the granular layer of both wild-type and Lor−/− epidermis.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2192642&req=5

Figure 8: Increased repetin expression in Lor−/− mice. (A) Staining of back skin from a newborn wild-type mouse with antibodies against repetin (green) and K14 (red). Overlapping expression of both proteins results in yellow fluorescence. Note the focal expression pattern and lack of accumulation in the stratum corneum. (B) Staining of Lor−/− neonatal back skin. Note the more uniform expression pattern and the presence of repetin at the periphery of corneocytes in the stratum corneum. Also, note the apparent accumulation of repetin in granules in the granular layer of both wild-type and Lor−/− epidermis.
Mentions: We also examined the expression of repetin by RPA. Repetin is a relatively new member of the “fused gene” S100 subgroup consisting of profilaggrin, trichohyalin, and repetin (Krieg et al. 1997). Repetin also shares homology with CE components and was recently shown to be upregulated along with SPRRP2A in another knockout mouse exhibiting a barrier defect (Segre et al. 1999). Repetin transcripts were increased approximately threefold at E17.5, twofold in newborns, and fourfold in 4-d-old Lor−/− back skin when compared with controls (Fig. 7 B). We were also able to demonstrate an increase in repetin in Lor−/− epidermis at the protein level by immunofluorescence microscopy. In wild-type epidermis, repetin is expressed focally, and it appears to be localized in granules. There is no obvious accumulation in the stratum corneum (Fig. 8 A). However, in Lor−/− epidermis, repetin is expressed more uniformily, and it appears to localize at the periphery of CE in the stratum corneum (Fig. 8 B).

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