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Molecular and Cellular Biology, August 2002, p. 5846-5858, Vol. 22, No. 16
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.16.5846-5858.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Suprabasal Desmoglein 3 Expression in the Epidermis of Transgenic Mice Results in Hyperproliferation and Abnormal Differentiation

Anita J. Merritt, Mohamed Y. Berika,,{dagger} Wenwu Zhai,,{ddagger} Sarah E. Kirk, Baijing Ji, Matthew J. Hardman, and David R. Garrod*

School of Biological Sciences, University of Manchester, Manchester, United Kingdom

Received 28 December 2001/ Returned for modification 5 March 2002/ Accepted 22 May 2002

The desmoglein 1 (Dsg1) and desmocollin 1 (Dsc1) isoforms of the desmosomal cadherins are expressed in the suprabasal layers of epidermis, whereas Dsg3 and Dsc3 are more strongly expressed basally. This differential expression may have a function in epidermal morphogenesis and/or may regulate the proliferation and differentiation of keratinocytes. To test this hypothesis, we changed the expression pattern by overexpressing human Dsg3 under the control of the keratin 1 (K1) promoter in the suprabasal epidermis of transgenic mice. From around 12 weeks of age, the mice exhibited flaking of the skin accompanied by epidermal pustules and thinning of the hair. Histological analysis of affected areas revealed acanthosis, hypergranulosis, hyperkeratosis, localized parakeratosis, and abnormal hair follicles. This phenotype has some features in common with human ichthyosiform diseases. Electron microscopy revealed a mild epidermal spongiosis. Suprabasally, desmosomes showed incorporation of the exogenous protein by immunogold labeling but were normal in structure. The epidermis was hyperproliferative, and differentiation was abnormal, demonstrated by expression of K14 in the suprabasal layer, restriction of K1, and strong induction of K6 and K16. The changes resembled those found in previous studies in which growth factors, cytokines, and integrins had been overexpressed in epidermis. Thus our data strongly support the view that Dsg3 contributes to the regulation of epidermal differentiation. Our results contrast markedly with those recently obtained by expressing Dsg3 in epidermis under the involucrin promoter. Possible reasons for this difference are considered in this paper.

* Corresponding author. Mailing address: School of Biological Sciences, 3.239 Stopford Building, University of Manchester, Oxford Rd., Manchester M13 9PT, United Kingdom. Phone: 44 161 275 5243. Fax: 44 161 275 3915. E-mail: david.garrod{at}man.ac.uk.

{dagger} Present address: Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

{ddagger} Present address: Lung Biology Center, University of California, San Francisco, San Francisco, CA 94143.

Molecular and Cellular Biology, August 2002, p. 5846-5858, Vol. 22, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.16.5846-5858.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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