Disease relevance of Krt4

• As mutations in K4 in humans lead to a disorder called white sponge nevus, the K4-deficient mice may serve as models for white sponge nevus and for understanding the role of K4 in cellular proliferation and differentiation [1].
• Positive reaction was obtained for CK4, CK34betaE12, CK10, CK14 in skin and cholesteatoma epithelium [2].
• In contrast, basal cell epithelioma, cloacogenic carcinoma, and squamous cell carcinoma of skin, tongue, and esophagus appeared negative with CK1-CK4 but positive with the other two antibodies [3].

High impact information on Krt4

• These results are consistent with the notion that K4 is required for internal epithelial cell integrity [1].
• Homozygous mice that do not express K4 develop a spectrum of phenotypes that affect several organs which express K4 including the esophagus, tongue, and cornea [1].
• Another clone, CK4, derived from CBA/N mice and having specificity against KLH plus I-Ak determinant could activate both CBA/N and NBF1 male B cells into IgM- and IgG-producing cells in the absence of KLH, and monoclonal anti-I-Ak antibody specifically blocked such activation [4].
• Expression of K12 in the cornea and K4 in the conjunctiva was impaired in the IKKalpha(-/-) mice [5].
• However, all the ras-transfected cell lines gave rise to colonies in soft agar while only 2 HPV-33-transfected lines (CK1 and CK4) displayed this property [6].

Biological context of Krt4

• 5. (3) Down-regulation during the E11.5 and E13.5 period (down-down-up), such as RHCG and keratin 4 [7].
• Some superficial corneal epithelial cells also expressed K4 during embryonic development, but by immunofluorescence microscopic criteria, this keratin was localized exclusively to the conjunctiva in post-natal and adult eye [8].
• We identified a missense mutation in mutant animals that predicts an N154S amino-acid substitution in the 1A domain of Keratin 4 (encoded by the Krt2-4 gene), a region known to be mutated in human patients with white sponge nevus (WSN) [9].

Anatomical context of Krt4

• From embryonic day 16 on K4 was detected in all areas of developing conjunctival epithelium [8].
• K4 was first observed, in 14 and 15 day embryos, in a subpopulation of epithelial cells which had invaginated from surface ectoderm to form the lid buds [8].
• Middle ear mucosa specimens revealed positive immunoreactivity with the antibodies against CK4 [2].
• Other squamous cell carcinomas derived from epiglottis and cervix uteri showed a mixture of positive and negative cells when tested with CK1-CK4, although all tumor cells were positive when tested with KG8.13 and with kerA [3].
• Cytokertains 3 and 17, which stained the entire corneal epithelium, were not detected, whereas cytokeratin 4, 5 and 13 were expressed [10].

Associations of Krt4 with chemical compounds

• RESULTS: Retinoic acid caused immunohistochemical diminution of keratin 4, keratin 13, and desmoglein [11].
• Characteristic keratin peptides, keratin 4 and 13, for mucosal epithelium were obviously expressed in the suprabasal cells, and keratohyalin granules and involucrin were present in the surface flat cells in the multilayered culture [12].

Other interactions of Krt4

• Similarly to K4, K14 was first noted in epithelium comprising the lid bud at embryonic day 14 [8].
• Expression of keratins K12, K4 and K14 during development of ocular surface epithelium [8].
• In contrast to what we found in internal stratified epithelia, however, K13 was expressed without its commonly encountered type II 57-kDa partner, K4 [13].

Analytical, diagnostic and therapeutic context of Krt4

• We examined the role of keratin 4 (K4) in maintaining the integrity of internal epithelial linings by using gene targeting to generate mice containing a null mutation in the epithelial K4 gene [1].
• METHODS: Ultrastructures of GE1 cells were observed and immunohistochemistry was used to detect keratin 4, keratin 13, and desmoglein expression [11].

References