Function of keratin 17 in epithelial tissues

2006 2006

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Abstract (summary)

One of the largest gene families in mammalian genomes encode the keratins, which form 10-12 nm wide cytoplasmic intermediate filaments in epithelial cells. Of the ∼50 known keratin genes, nearly two-thirds are expressed in overlapping patterns in the hair follicle. Inactivating the mouse keratin 17 gene gives rise to, in a reversible and strain-dependent fashion, severe phenotypic alterations restricted to hair follicles (alopecia). This presentation is surprisingly mild given the wide distribution of K17 and the presentation of patients whose genomes harbor missense K17 alleles. We can account for these findings based on the occurrence of compensation by proteins highly related to K17, including K16 (in hair tissue and oral mucosa), K14 (in sweat glands), and a newly discovered type I keratin, K17n (in nail).

The alopecia phenotype of K17 null mice correlates with hair fragility and apoptosis in hair-producing matrix cells. We demonstrate that this apoptosis reflects a premature entry into catagen, which is the regression stage of hair cycle. In primary culture, K17 null keratinocytes are more sensitive to TNFα-induced, but not other, pro-apoptosic challenges. TNFα also elicits slightly more NF-κB activation in K17 null keratinocytes compared to wild type. The ability of K17 to interact with TRADD in vivo provides a potential mechanistic basis for this effect. We show that mice null for TNFα exhibit a delay in executing this transition from anagen to catagen and compound loss of TNFα partially prevents apoptosis that normally occurs in K17 null hair follicles. Our data reveal novel roles of K17 and TNFα during hair cycling in addition to showing that K17 attenuates TNFα signaling in vivo.

Indexing (details)

Cellular biology;
Anatomy & physiology;
0379: Cellular biology
0433: Anatomy & physiology
0433: Animals
Identifier / keyword
Biological sciences; Epithelial; Intermediate filament; Keratin 17; TNF-alpha
Function of keratin 17 in epithelial tissues
Tong, Xuemei
Number of pages
Publication year
Degree date
School code
DAI-B 67/04, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
054264522X, 9780542645228
Coulombe, Pierre A.
The Johns Hopkins University
University location
United States -- Maryland
Source type
Dissertations & Theses
Document type
Dissertation/thesis number
ProQuest document ID
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
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