Cathepsin L deficiency as molecular defect offurless:hyperproliferation of keratinocytes and pertubation of hair follicle cycling
| Autor: | Peter J. Schmidt, Jan M. Deussing, Christoph Peters, Paul Saftig, A. Hafner, Wolfgang W. Schmahl, Vladimir A. Botchkarev, Ingrun Anton-Lamprecht, Ralf Paus, Wera Roth, Meike Pauly-Evers, Johanna Scherer, Kurt von Figura |
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| Rok vydání: | 2000 |
| Předmět: |
Keratinocytes
Periodicity medicine.medical_specialty Cathepsin L Antigen presentation Acanthosis Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Internal medicine Endopeptidases otorhinolaryngologic diseases Genetics medicine Animals Molecular Biology 030304 developmental biology 0303 health sciences Hyperplasia integumentary system biology Gene targeting Alopecia Epithelial Cells Keratosis medicine.disease Hair follicle Cathepsins Mice Mutant Strains Cell biology Cysteine Endopeptidases Hair follicle morphogenesis Endocrinology medicine.anatomical_structure Hair loss 030220 oncology & carcinogenesis Hair Disorder Mutation Mutagenesis Site-Directed biology.protein sense organs Epidermis Hair Follicle Cell Division Biotechnology |
| Zdroj: | The FASEB Journal. 14:2075-2086 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.99-0970com |
| Popis: | Lysosomal cysteine proteinases of the papain family are involved in lysosomal bulk proteolysis, major histocompatibility complex class II mediated antigen presentation, prohormone processing, and extracellular matrix remodeling. Cathepsin L (CTSL) is a ubiquitously expressed major representative of the papain-like family of cysteine proteinases. To investigate CTSL in vivo functions, the gene was inactivated by gene targeting in embryonic stem cells. CTSL-deficient mice develop periodic hair loss and epidermal hyperplasia, acanthosis, and hyperkeratosis. The hair loss is due to alterations of hair follicle morphogenesis and cycling, dilatation of hair follicle canals, and disturbed club hair formation. Hyperproliferation of hair follicle epithelial cells and basal epidermal keratinocytes-both of ectodermal origin-are the primary characteristics underlying the mutant phenotype. Pathological inflammatory responses have been excluded as a putative cause of the skin and hair disorder. The phenotype of CTSL-deficient mice is reminiscent of the spontaneous mouse mutant furless (fs). Analyses of the ctsl gene of fs mice revealed a G149R mutation inactivating the proteinase activity. CTSL is the first lysosomal proteinase shown to be essential for epidermal homeostasis and regular hair follicle morphogenesis and cycling. |
| Databáze: | OpenAIRE |
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