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Development of ichthyosiform skin compensates for defective permeability barrier function in mice lacking transglutaminase 1.

ABSTRACT: Transglutaminase 1 (TGase 1) is one of the genes implicated in autosomal recessive congenital ichthyosis. Skin from TGase 1(-/-) mice, which die as neonates, lacks the normal insoluble cornified envelope and has impaired barrier function. Characterization of in situ dye permeability and transepidermal water loss revealed defects in the development of the skin permeability barrier in TGase 1(-/-) mice. In the stratum corneum of the skin, tongue, and forestomach, intercellular lipid lamellae were disorganized, and the corneocyte lipid envelope and cornified envelope were lacking. Neonatal TGase 1(-/-) mouse skin was taut and erythrodermic, but transplanted TGase 1(-/-) mouse skin resembled that seen in severe ichthyosis, with epidermal hyperplasia and marked hyperkeratosis. Abnormalities in those barrier structures remained, but transepidermal water loss was improved to control levels in the ichthyosiform skin. From these results, we conclude that TGase 1 is essential to the assembly and organization of the barrier structures in stratified squamous epithelia. We suggest that the ichthyosiform skin phenotype in TGase 1 deficiency develops the massive hyperkeratosis as a physical compensation for the defective cutaneous permeability barrier required for survival in a terrestrial environment.

SUBMITTER: Kuramoto N

PROVIDER: S-EPMC150837 | biostudies-literature | 2002 Jan

REPOSITORIES: biostudies-literature

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Development of ichthyosiform skin compensates for defective permeability barrier function in mice lacking transglutaminase 1.

Kuramoto Nobuo N Takizawa Toshihiro T Takizawa Takami T Matsuki Masato M Morioka Hiroyuki H Robinson John M JM Yamanishi Kiyofumi K

The Journal of clinical investigation 20020101 2

Transglutaminase 1 (TGase 1) is one of the genes implicated in autosomal recessive congenital ichthyosis. Skin from TGase 1(-/-) mice, which die as neonates, lacks the normal insoluble cornified envelope and has impaired barrier function. Characterization of in situ dye permeability and transepidermal water loss revealed defects in the development of the skin permeability barrier in TGase 1(-/-) mice. In the stratum corneum of the skin, tongue, and forestomach, intercellular lipid lamellae were ...[more]

PMID: 11805136

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Project description:Our objective was to characterize the mechanisms by which local burn injury compromises epithelial barrier function in burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue.Experimental mouse scald burn injury.University Research Laboratory.C57/Bl6 Male mice, 8-12 weeks old.To confirm that dehydration was not contributing to our observed barrier defects, in some experiments mice received 1 mL of saline fluid immediately after burn, while a subgroup received an additional 0.5 mL at 4 hours and 1 mL at 24 hours following burn. We then assessed skin pH and transepidermal water loss every 12 hours on the burn wounds for 72 hours postburn.Burn margin exhibited increased epidermal barrier permeability indicated by higher pH, greater transepidermal water loss, and reduced lipid synthesis enzyme expression and structural protein production up to 96 hours postburn. By contrast, antimicrobial peptide production and protease activity were elevated in burn margin. Skin extracts from burn margin did not exhibit changes in the ability to inhibit bacterial growth. However, distal unburned skin from burned mice also demonstrated an impaired response to barrier disruption, indicated by elevated transepidermal water loss and reduced lipid synthesis enzyme and structural protein expression up to 96 hours postburn. Furthermore, skin extracts from distal unburned skin exhibited greater protease activity and a reduced capacity to inhibit bacterial growth of several skin pathogens. Finally, we established that antimicrobial peptide levels were also altered in the lung and bladder, which are common sites of secondary infection in burn-injured patients.These findings reveal several undefined deficiencies in epithelial barrier function at the burn margin, potential donor skin sites, and organs susceptible to secondary infection. These functional and biochemical data provide novel insights into the mechanisms for graft failure and secondary infection after burn injury.

Dataset Information

Development of ichthyosiform skin compensates for defective permeability barrier function in mice lacking transglutaminase 1.

Publications

Development of ichthyosiform skin compensates for defective permeability barrier function in mice lacking transglutaminase 1.

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