Limits...
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.

Show MeSH

Related in: MedlinePlus

Analysis of mouse Dsg 3 expression in transgenic and normal mouse skin. (A) Immunoblot with anti–FLAG antibody indicates expression of mouse Dsg 3-FLAG (arrowhead, ∼160 kD) in extract of transgenic (+) mouse skin. Nontransgenic littermate (−) skin serves as a control. (B) Immunofluorescence of transgenic mouse tail skin for FLAG epitope shows expression of transgene in suprabasilar area of epidermis. (C) Immunofluorescence of nontransgenic mouse tail for mouse Dsg 3 shows expression in the basal and immediate suprabasal layer of epidermis. (D) Immunofluorescence of transgenic mouse tail for mouse Dsg 3 shows expression throughout the epidermis. (B–D) Original magnification 100×. (E) Immunoblotting for mouse Dsg 3 and mouse Dsg 1 from extracts of mouse skin and tongue show that transgenic (scaly) epidermis from founder 1 has a Dsg 3/Dsg 1 ratio similar to normal tongue mucous membrane, whereas transgenic mucous membrane from the same founder expresses excess Dsg 3.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2169464&req=5

Figure 2: Analysis of mouse Dsg 3 expression in transgenic and normal mouse skin. (A) Immunoblot with anti–FLAG antibody indicates expression of mouse Dsg 3-FLAG (arrowhead, ∼160 kD) in extract of transgenic (+) mouse skin. Nontransgenic littermate (−) skin serves as a control. (B) Immunofluorescence of transgenic mouse tail skin for FLAG epitope shows expression of transgene in suprabasilar area of epidermis. (C) Immunofluorescence of nontransgenic mouse tail for mouse Dsg 3 shows expression in the basal and immediate suprabasal layer of epidermis. (D) Immunofluorescence of transgenic mouse tail for mouse Dsg 3 shows expression throughout the epidermis. (B–D) Original magnification 100×. (E) Immunoblotting for mouse Dsg 3 and mouse Dsg 1 from extracts of mouse skin and tongue show that transgenic (scaly) epidermis from founder 1 has a Dsg 3/Dsg 1 ratio similar to normal tongue mucous membrane, whereas transgenic mucous membrane from the same founder expresses excess Dsg 3.

Mentions: Expression of the transgene was detected by Western blotting for the FLAG-tagged mouse Dsg 3 of extracted skin from transgenic neonatal mice (Fig. 2 A). Distribution of expression of the transgenic mouse Dsg 3-FLAG was detected by immunofluorescence with anti–FLAG antibodies of mouse skin, which showed cell-surface staining in the suprabasilar layers of the epidermis (Fig. 2 B). The distribution of both transgenic and nontransgenic Dsg 3 in mouse skin was detected by immunofluorescence with an anti–mouse Dsg 3 antibody. Whereas nontransgenic littermates showed Dsg 3 only in the deep epidermis (Fig. 2 C), transgenic animals showed Dsg 3 throughout the entire epidermis (Fig. 2 D), in a pattern identical to that described in oral mucous membrane (Mahoney et al. 1999).


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)

Analysis of mouse Dsg 3 expression in transgenic and normal mouse skin. (A) Immunoblot with anti–FLAG antibody indicates expression of mouse Dsg 3-FLAG (arrowhead, ∼160 kD) in extract of transgenic (+) mouse skin. Nontransgenic littermate (−) skin serves as a control. (B) Immunofluorescence of transgenic mouse tail skin for FLAG epitope shows expression of transgene in suprabasilar area of epidermis. (C) Immunofluorescence of nontransgenic mouse tail for mouse Dsg 3 shows expression in the basal and immediate suprabasal layer of epidermis. (D) Immunofluorescence of transgenic mouse tail for mouse Dsg 3 shows expression throughout the epidermis. (B–D) Original magnification 100×. (E) Immunoblotting for mouse Dsg 3 and mouse Dsg 1 from extracts of mouse skin and tongue show that transgenic (scaly) epidermis from founder 1 has a Dsg 3/Dsg 1 ratio similar to normal tongue mucous membrane, whereas transgenic mucous membrane from the same founder expresses excess Dsg 3.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Analysis of mouse Dsg 3 expression in transgenic and normal mouse skin. (A) Immunoblot with anti–FLAG antibody indicates expression of mouse Dsg 3-FLAG (arrowhead, ∼160 kD) in extract of transgenic (+) mouse skin. Nontransgenic littermate (−) skin serves as a control. (B) Immunofluorescence of transgenic mouse tail skin for FLAG epitope shows expression of transgene in suprabasilar area of epidermis. (C) Immunofluorescence of nontransgenic mouse tail for mouse Dsg 3 shows expression in the basal and immediate suprabasal layer of epidermis. (D) Immunofluorescence of transgenic mouse tail for mouse Dsg 3 shows expression throughout the epidermis. (B–D) Original magnification 100×. (E) Immunoblotting for mouse Dsg 3 and mouse Dsg 1 from extracts of mouse skin and tongue show that transgenic (scaly) epidermis from founder 1 has a Dsg 3/Dsg 1 ratio similar to normal tongue mucous membrane, whereas transgenic mucous membrane from the same founder expresses excess Dsg 3.
Mentions: Expression of the transgene was detected by Western blotting for the FLAG-tagged mouse Dsg 3 of extracted skin from transgenic neonatal mice (Fig. 2 A). Distribution of expression of the transgenic mouse Dsg 3-FLAG was detected by immunofluorescence with anti–FLAG antibodies of mouse skin, which showed cell-surface staining in the suprabasilar layers of the epidermis (Fig. 2 B). The distribution of both transgenic and nontransgenic Dsg 3 in mouse skin was detected by immunofluorescence with an anti–mouse Dsg 3 antibody. Whereas nontransgenic littermates showed Dsg 3 only in the deep epidermis (Fig. 2 C), transgenic animals showed Dsg 3 throughout the entire epidermis (Fig. 2 D), in a pattern identical to that described in oral mucous membrane (Mahoney et al. 1999).

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