Disease relevance of Krt5

• We suggest that K5 null mutations may be lethal in human epidermolysis bullosa simplex patients [1].
• Nulliparous transgenic females developed mammary hyperplasia that comprised undifferentiated basal (K5/14-positive, K8- and alpha-smooth muscle-actin-negative) cells [2].
• Antibodies to the basal cell keratins, K5 and K14, stained both basal and suprabasal cells in hyperplastic epidermis and papillomas [3].
• In addition, as a consequence of transgene expression in other ectodermally derived epithelia, K5-GR mice exhibited further abnormalities that strikingly resemble the clinical findings in patients with ectodermal dysplasia, which includes aplasia cutis congenita [4].
• Inducible expression of a mutated K-ras gene under the control of the K5 promoter led to the development of hyperplastic and dysplastic epithelial lesions and carcinomas, with an incidence of 100% and a minimum latency of a week [5].

High impact information on Krt5

• This study describes abnormalities of the thymus in mice in which the Stat3 gene has been specifically disrupted behind the keratin 5 promoter [6].
• METHODS: The pathologic changes of transgenic mouse pancreas with keratin 5-promoter-driven expression and activity of COX-2 were characterized [7].
• Surprisingly, our transgenic mice expressing wild-type TGFbeta1 in the epidermis using a keratin 5 promoter (K5.TGFbeta1(wt)) developed inflammatory skin lesions, with gross appearance of psoriasis-like plaques, generalized scaly erythema, and Koebner's phenomenon [8].
• Transfection of K10 in combination with K5 or K1 resulted in cytoplasmic agglomerates, but not a cytoskeleton [9].
• Keratinocyte-specific expression of the transgene was achieved by using a keratin 5 promoter [10].

Biological context of Krt5

• Thymus Medulla Formation and Central Tolerance Are Restored in IKK{alpha}-/- Mice That Express an IKK{alpha} Transgene in Keratin 5+ Thymic Epithelial Cells [11].
• In contrast to the K14(-/-) mice, we detected a strong induction of the wound-healing keratin K6 in the suprabasal epidermis of cytolyzed areas of postnatal K5(-/-) mice [1].
• We have focused on tooth development in K5-GR mice and found that an inhibitor of steroid synthesis partially reversed the abnormal phenotype [12].
• We have used a recently described model in which a ras oncogene is expressed in cytokeratin 5 (K5)-expressing cells on doxycycline administration to explore the effects of this oncogene in salivary glands of adult mice [5].
• To explore the emergence of TEC subsets during ontogeny, we analyzed keratin 8 and keratin 5 expression at several stages of fetal development in normal C57BL/6J mice [13].

Anatomical context of Krt5

• Moreover, we show that in the absence of K5 and other type II keratins, residual K14 and K15 aggregated along hemidesmosomes, demonstrating that individual keratins without a partner are stable in vivo [1].
• The levels of K15 and K16 were not different in the MKC-5 and MKC-6 cell lines, suggesting that they are not contributing factors to the stabilization of K5 in the mutant cells [14].
• K5/14 persisted suprabasally at elevated protein levels, whereas their mRNAs remained restricted to the basal keratinocytes [15].
• Here, we report that K5-GR mice exhibit multiple epithelial defects in hair follicle, tooth, and palate development [12].
• K5 protein expression starts in the forelimb surface ectoderm as early as E9.25, while the expression of its partner, K14, begins at E9.75 [16].

Associations of Krt5 with chemical compounds

• Early vitamin A deficiency caused the appearance of single subcolumnar reserve cells expressing K5 mRNA [17].
• In the study presented here, the effects of constitutive COX-2 overexpression in keratin 5-positive myoepithelial and luminal cells, driven by the keratin 5 promoter in a hormone-independent manner, was investigated [18].
• [3H]ATMP failed to bind to K5 after removal of GlcNAc [19].
• K5 failed to bind to ATMP when the third proline was substituted with threonine, as in some cases of human X-linked amelogenesis imperfecta or when tyrosyl residues were substituted with phenylalanine [19].
• Immunohistochemistry revealed that the CD44(+) cancer cells have a primitive cellular morphology and costain with the basal cell marker Cytokeratin 5/14, whereas the CD44(-) cancer cells resemble differentiated squamous epithelium and express the differentiation marker Involucrin [20].

Other interactions of Krt5

• The distribution of K5, the natural partner of K14, at the immunofluorescence level was also normal looking in the K14-/- MKC-5 cells, but with fewer filaments detectable, consistent with the approximately 20% reduction in K5 detectable on immunoblots [14].
• The localization of both K5 and K1 proteins in these same cell layers, and above, is consistent with transcriptional regulation of these keratins [17].
• From E9.25 to E9.75, K5 forms atypical filaments with K18 [16].
• While CK5 expression in Wnt10b transgenic tissue was still confined to the lining cell layer, its expression in Int2 transgenic tissue was completely disorganized [21].
• K5 was much stronger in the conjunctiva of the IKKalpha(-/-) mice [22].

Analytical, diagnostic and therapeutic context of Krt5

• Cystic duct dilatations and proliferative epithelial lesions in mouse mammary glands upon keratin 5 promoter-driven overexpression of cyclooxygenase-2 [18].
• One- and two-dimensional western blot analysis showed that this new cytokeratin was 57 kDa in size and ran slightly below the area of cytokeratin 5, which corresponded to that of the cytokeratin 6 family members [23].
• K5 and EGFP expression increased in parallel in burned K5GFP mice as demonstrated by confocal microscopy [24].
• We used a mouse model of sex-mismatched tracheal transplantation and found that CK5+ circulating progenitor epithelial cells contribute to re-epithelialization of the airway and re-establishment of the pseudostratified epithelium [25].
• An average of 68% suppression of primary tumor growth was observed in the K5-treated mice compared with control group [26].

References