Disease relevance of Krt19

• Hence, mouse gallbladder K8/K18/K19 expression is induced in response to cholelithiasis injury [1].
• Notably, we found mucous cell metaplasia in the glandular stomach of the K19-Wnt1/C2mE mice as early as 5 weeks of age, before the dysplastic tumor development [2].
• RESULTS: Aberrant expression of COX-2 in a few ductal cells and COX-2-mediated PG synthesis in the transgenic mice resulted in keratin 19- and mucin-positive intraductal papillary mucinous neoplasm- and pancreatic intraepithelial neoplasia-like structures, characterized by an increased proliferation index and serous cystadenomas [3].
• These results suggest that CK19 may play an important role in HCC metastasis [4].
• Our results suggest that keratin 19 in fast-twitch skeletal muscle helps organize costameres and links them to the contractile apparatus, and that the absence of keratin 19 disrupts these structures, resulting in loss of contractile force, altered distribution of mitochondria and mild myopathy [5].

High impact information on Krt19

• Keratin filaments could be visualized in each line by indirect immunofluorescence with the use of polyclonal or monoclonal antibodies to keratins; staining with monospecific antibodies indicated that 3 of the 4 lines expressed simple epithelial keratins 8 and 18, whereas 1 of the 4 also expressed keratin 19 [6].
• Pancreatic ductal cells (PDCs) were purified from cytokeratin 19 (K19)-Ki-RAS(G12V) transgenic mice and control littermates to identify properties of Ki-Ras activation in a cell-type-specific context [7].
• Presence of antisense resulted in loss of CK19 immunoreactivity of the bipotential stem cells [8].
• The lethality resulted from defects in the placenta where both K19 and K8 are normally expressed [9].
• The expression of basal/intermediate marker CK 19 in three FACS areas, g1, g2, and g3, gated according to cellular size and granularity, was 1:0.6:2 in WT and 1:4:6.7 in ER beta(-/-) mice, showing a shift of CK 19-positive cells toward a cell population of intermediate size and granularity [10].

Biological context of Krt19

• Using probes corresponding to highly conserved sequences in intermediate filament proteins, we mapped two other genes downstream from the K19 gene [11].
• We report here the cloning and mapping of a 55-kb region surrounding the keratin 19 (K19) gene in the mouse genome [11].
• Finally, we showed that an antibody widely used in studies of the cell lineages of hepatic and pancreatic tissues and their neoplasms, the mouse monoclonal antibody OV-6, recognizes a common epitope in K14 and K19 [12].
• One clone of 16 kb contained the second to the sixth exons of K19 and the other keratin-encoding gene was located about 4 kb downstream from K19 [13].
• The present observations confirm that downregulation of K19 gene expression in the fetal testis is one of the earliest molecular events attesting the commitment of the undifferentiated gonad to the male differentiative pathway [14].

Anatomical context of Krt19

• Keratin 14 protein in cultured nonparenchymal rat hepatic epithelial cells: characterization of keratin 14 and keratin 19 as antigens for the commonly used mouse monoclonal antibody OV-6 [12].
• K19 disappears as Sertoli cells differentiate [14].
• Over 60% of colonies derived from E14.5 Dlk+ cells contained both albumin+ and cytokeratin 19+ cells, indicating that a majority of colony-forming Dlk+ cells are able to differentiate into both hepatocyte and biliary epithelial cell lineages [15].
• All the cell lines synthesize anomalously simple epithelial keratins, substantial amounts of K8, and minor quantities of K18 and K19, but the level of expression is increased in PDVC57 [16].
• Keratin 21 was detected exclusively in differentiated villus cells and in goblet, enteroendocrine, and Paneth cells in the crypts; in the proliferative crypt cells keratin 19 was predominant [17].

Associations of Krt19 with chemical compounds

• Immunohistochemistry was performed using anti-c-kit, OV6, Thy1, CK19, AFP, vWF and Rab3b [18].
• Cells of the clonal cell lines do not grow in soft agar and are nontumorigenic, and they express cytokeratin 19, A6 antigen, and alpha6 integrin, as well as a large panel of hepatocyte functions [19].

Regulatory relationships of Krt19

• At an intermediate stage, nestin is partially co-expressed with C-peptide and cytokeratin 19, whereas islet-like clusters at the terminal stage are nestin-negative [20].

Other interactions of Krt19

• The acidic keratins K18 and K19 have been shown to display a sex-specific expression during gonadal differentiation in the rat [14].
• The heads of embryos were processed by standard immunohistochemistry with antipancytokeratin (KAE1), antikeratins 18 (K18) and 19 (K19), antivimentin, and anti E-cadherin antibodies [21].
• K8, K19, and vimentin were undetectable in both lines [22].
• However these progenitors were CK-19-positive (biliary and bipotential progenitor marker) only in the presence of FGF1 or FGF4 and not FGF8 [23].
• We conclude that expression of nestin and cytokeratin 19 is a normal property of ES cells preceding differentiation into C-peptide/insulin-producing cells without any selection for nestin-positive phenotypes [20].

Analytical, diagnostic and therapeutic context of Krt19

• We found that Sca-1(+) BMCs gave rise to adherent hepatic-like cells, which expressed albumin as assessed with immunocytochemistry and RNA-polymerase chain reaction (PCR), and alpha-fetoprotein and cytokeratin 19 as examined with RNA-PCR [24].
• The epithelial origin was confirmed by positive cytokeratin 19 staining for these cells and the presence of microvilli and tight junctions under electron microscopy [25].
• RT-PCR and gene electrophoresis successfully detected CD31 and Beta-Actin molecules with minimal Keratin 19 expression, which served as the negative control [26].

References