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Desmoglein isoform distribution affects stratum corneum structure and function.

Elias PM, Matsuyoshi N, Wu H, Lin C, Wang ZH, Brown BE, Stanley JR - J. Cell Biol. (2001)

Bottom Line: Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes.This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping.These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of California San Francisco, San Francisco, California 94143, USA.

ABSTRACT
Desmogleins are desmosomal cadherins that mediate cell-cell adhesion. In stratified squamous epithelia there are two major isoforms of desmoglein, 1 and 3, with different distributions in epidermis and mucous membrane. Since either desmoglein isoform alone can mediate adhesion, the reason for their differential distribution is not known. To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter. These mice expressed desmoglein 3 with the same distribution in epidermis as found in normal oral mucous membranes, while expression of other major differentiation molecules was unchanged. Although the nucleated epidermis appeared normal, the epidermal stratum corneum was abnormal with gross scaling, and a lamellar histology resembling that of normal mucous membrane. The mice died shortly after birth with severe dehydration, suggesting excessive transepidermal water loss, which was confirmed by in vitro and in vivo measurement. Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes. This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping. These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

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Involucrin-Dsg 3 transgenic mice show increased transepidermal water loss. (A) Neonatal mice were separated from their mothers and weighed over time. Transgenic mice (♦) lose weight faster than nontransgenic littermates (•). Error bars indicate SEM for four mice in each group. Rate of weight loss, mean ± SEM is shown. (B) Weight loss of isolated skin from transepidermal water loss through the epidermis. Graphs show paired comparison of transgenic mouse skin (♦) and nontransgenic littermate skin (▪). Rate of transepidermal water loss, mean ± SEM for eight samples in each group is shown.
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Figure 4: Involucrin-Dsg 3 transgenic mice show increased transepidermal water loss. (A) Neonatal mice were separated from their mothers and weighed over time. Transgenic mice (♦) lose weight faster than nontransgenic littermates (•). Error bars indicate SEM for four mice in each group. Rate of weight loss, mean ± SEM is shown. (B) Weight loss of isolated skin from transepidermal water loss through the epidermis. Graphs show paired comparison of transgenic mouse skin (♦) and nontransgenic littermate skin (▪). Rate of transepidermal water loss, mean ± SEM for eight samples in each group is shown.

Mentions: To test this hypothesis, we first isolated 7-d-old transgenic and nontransgenic littermates from their mothers and weighed them for 5 h (Fig. 4 A). In all cases, transgenic mice lost weight faster than nontransgenic mice. Presumably this accelerated weight loss of transgenic mice could be ascribed to increased transepidermal water loss. However, it is possible that other fluid loss (e.g., urine) could have accounted for these differences, although no other evidence of fluid loss was apparent.


Desmoglein isoform distribution affects stratum corneum structure and function.

Elias PM, Matsuyoshi N, Wu H, Lin C, Wang ZH, Brown BE, Stanley JR - J. Cell Biol. (2001)

Involucrin-Dsg 3 transgenic mice show increased transepidermal water loss. (A) Neonatal mice were separated from their mothers and weighed over time. Transgenic mice (♦) lose weight faster than nontransgenic littermates (•). Error bars indicate SEM for four mice in each group. Rate of weight loss, mean ± SEM is shown. (B) Weight loss of isolated skin from transepidermal water loss through the epidermis. Graphs show paired comparison of transgenic mouse skin (♦) and nontransgenic littermate skin (▪). Rate of transepidermal water loss, mean ± SEM for eight samples in each group is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2169464&req=5

Figure 4: Involucrin-Dsg 3 transgenic mice show increased transepidermal water loss. (A) Neonatal mice were separated from their mothers and weighed over time. Transgenic mice (♦) lose weight faster than nontransgenic littermates (•). Error bars indicate SEM for four mice in each group. Rate of weight loss, mean ± SEM is shown. (B) Weight loss of isolated skin from transepidermal water loss through the epidermis. Graphs show paired comparison of transgenic mouse skin (♦) and nontransgenic littermate skin (▪). Rate of transepidermal water loss, mean ± SEM for eight samples in each group is shown.
Mentions: To test this hypothesis, we first isolated 7-d-old transgenic and nontransgenic littermates from their mothers and weighed them for 5 h (Fig. 4 A). In all cases, transgenic mice lost weight faster than nontransgenic mice. Presumably this accelerated weight loss of transgenic mice could be ascribed to increased transepidermal water loss. However, it is possible that other fluid loss (e.g., urine) could have accounted for these differences, although no other evidence of fluid loss was apparent.

Bottom Line: Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes.This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping.These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of California San Francisco, San Francisco, California 94143, USA.

ABSTRACT
Desmogleins are desmosomal cadherins that mediate cell-cell adhesion. In stratified squamous epithelia there are two major isoforms of desmoglein, 1 and 3, with different distributions in epidermis and mucous membrane. Since either desmoglein isoform alone can mediate adhesion, the reason for their differential distribution is not known. To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter. These mice expressed desmoglein 3 with the same distribution in epidermis as found in normal oral mucous membranes, while expression of other major differentiation molecules was unchanged. Although the nucleated epidermis appeared normal, the epidermal stratum corneum was abnormal with gross scaling, and a lamellar histology resembling that of normal mucous membrane. The mice died shortly after birth with severe dehydration, suggesting excessive transepidermal water loss, which was confirmed by in vitro and in vivo measurement. Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes. This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping. These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

Show MeSH
Related in: MedlinePlus