Conditional targeting of plectin in prenatal and adult mouse stratified epithelia causes keratinocyte fragility and lesional epidermal barrier defects
Author:
Ackerl Reinhard1, Walko Gernot1, Fuchs Peter1, Fischer Irmgard1, Schmuth Matthias2, Wiche Gerhard1
Affiliation:
1. Department of Molecular Cell Biology, Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria 2. Department of Dermatology and Venereology, Medical University of Innsbruck, 6020 Innsbruck, Austria
Abstract
Plectin, a widespread intermediate filament-based cytolinker protein capable of interacting with a variety of cytoskeletal structures and plasma membrane-bound junctional complexes, serves essential functions in maintenance of cell and tissue cytoarchitecture. We have generated a mouse line bearing floxed plectin alleles and conditionally deleted plectin in stratified epithelia. This strategy enabled us to study the consequences of plectin deficiency in this particular type of tissues in the context of the whole organism without plectin loss affecting other tissues. Conditional knockout mice died early after birth, showing signs of starvation and growth retardation. Blistering was observed on their extremities and on the oral epithelium after initial nursing, impairing food uptake. Knockout epidermis was very fragile and showed focal epidermal barrier defects caused by the presence of small skin lesions. Stratification, proliferation and differentiation of knockout skin seemed unaffected by epidermis-restricted plectin deficiency. In an additionally generated mouse model, tamoxifen-induced Cre-ERT-mediated recombination led to mice with a mosaic plectin deletion pattern in adult epidermis, combined with microblister formation and epidermal barrier defects. Our study explains the early lethality of plectin-deficient mice and provides a model to ablate plectin in adult animals which could be used for developing gene or pharmacological therapies.
Publisher
The Company of Biologists
Reference36 articles.
1. Abrahamsberg, C., Fuchs, P., Osmanagic-Myers, S., Fischer, I., Propst, F., Elbe-Bürger, A. and Wiche, G. (2005). Targeted ablation of plectin isoform 1 uncovers role of cytolinker proteins in leukocyte recruitment. Proc. Natl. Acad. Sci. USA102, 18449-18454. 2. Andrä, K., Lassmann, H., Bittner, R., Shorny, S., Fässler, R., Propst, F. and Wiche, G. (1997). Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture. Genes Dev.11, 3143-3156. 3. Andrä, K., Nikolic, B., Stöcher, M., Drenckhahn, D. and Wiche, G. (1998). Not just scaffolding: plectin regulates actin dynamics in cultured cells. Genes Dev.12, 3442-3451. 4. Andrä, K., Kornacker, I., Jörgl, A., Zörer, M., Spazierer, D., Fuchs, P., Fischer, I. and Wiche, G. (2003). Plectin-isoform-specific rescue of hemidesmosomal defects in plectin (–/–) keratinocytes. J. Invest. Dermatol.120, 189-197. 5. Benitah, S. A., Frye, M., Glogauer, M. and Watt, F. M. (2005). Stem cell depletion through epidermal deletion of Rac1. Science309, 933-935.
Cited by
47 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|