Ectopic expression of desmin in the epidermis of transgenic mice permits development of a normal epidermis.
Cell architecture is largely based on the interaction of cytoskeletal proteins, which include intermediate filaments (IF), microfilaments, microtubules, as well as their type-specific membrane-attachment structures and associated proteins. In order to further our understanding of IF proteins and to address the fundamental issue whether different IF perform unique functions in different tissues, we expressed a desmin transgene in the basal epidermis of mice. Ectopic expression of desmin led to the formation of an additional, keratin-independent IF cytoskeleton and did not interfere with the keratin-desmosome interaction. We show that ectopic expression of a type III IF protein in basal keratinocytes did not interfere with the normal epidermal architecture and the program of terminal differentiation. This demonstrated that keratinocytes suffered no obvious detrimental effects from extra desmin filaments in their cytoplasm. In addition, we asked whether stable expression of desmin could rescue K5 null mice, which served as a model for severe EBS. Transgenic mice ectopically expressing desmin in the basal layer were mated with K5 heterozygous deficient animals to generate desmin rescue mice and analysed. In summary, our study support the notion that the different IF like desmin or keratins composing a IF network in vivo are central to cytoskeletal architecture and design in cells.
Kirfel
Jutta
J
Institute of Physiological Chemistry and Bonner Forum Biomedizin, University of Bonn, Nussallee 11, 53115 Bonn, Germany.
Peters
Bettina
B
Grund
Christine
C
Reifenberg
Kurt
K
Magin
Thomas M
TM
D000818:Animals; D003893:Desmin / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004817:Epidermis / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D016110:Epidermolysis Bullosa Simplex / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053547:Keratin-14; D015603:Keratinocytes / Q000378:metabolism / Q000648:ultrastructure; D007633:Keratins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype
D003893:Desmin; C507540:KRT14 protein, human; D053547:Keratin-14; C507446:Krt14 protein, mouse; D007633:Keratins