Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Keratins comprise a multigene family of structural proteins that form the 10-nm filaments present in epithelial cells. Keratin filament formation requires the presence of stoichiometric quantities of type I and type II keratin peptides. Each keratin peptide contains an N-terminal "head" segment, a C-terminal "tail" segment, and a highly conserved, alpha-helical central rod domain. To investigate the importance of these domains in situ, we have altered the DNA coding sequence of human cytokeratin K19 and transiently expressed the mutants in PtK2 cells that contain an endogenous keratin filament system. Interestingly, K19 mutants containing 4, 8, 12, and 24 amino acid insertions in the non-alpha-helical L1 region of the central rod domain successfully integrate into the endogenous PtK2 keratin filaments. Another K19 mutant, K19-bGAL, that encodes bacterial beta-galactosidase (bGAL) fused in phase to the 3' end of the K19 central rod domain, also integrates into the endogenous PtK2 keratin filaments. Our results demonstrate 1) that the spacing between the highly conserved amino and carboxy terminal ends of the K19 central rod domain can be increased without significantly effecting K19's ability to interact with keratin filaments and 2) that addition of a highly soluble 66-kDa tail to K19 does not impede its interaction with the filament system.
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PMID:Central rod domain insertion and carboxy-terminal fusion mutants of human cytokeratin K19 are incorporated into endogenous keratin filaments. 137 Feb 30

We have investigated the differentiation potential of propagable cultured rat pancreatic duct epithelial cells after in vivo implantation in isogeneic Fischer-344 rats. Cells genetically labeled with Escherichia coli beta-galactosidase (lacZ) reporter gene were embedded in a mixture of collagen and Matrigel (basement membrane matrix) and implanted either subcutaneously or intraperitoneally. Tissues from the two locations were harvested 4 to 8 weeks later. The great majority of the lacZ-labeled epithelial cells colonizing both sites phenotypically resembled hepatocytes, although they demonstrated different degrees of hepatocytic differentiation. Less than 5% of lacZ-labeled cells formed ductular structures. The hepatocyte-like cells from the subcutaneous implantation site expressed mixed phenotypes of both hepatocyte and ductal cell, including the expression of alpha-fetoprotein, tyrosine amino-transferase, gamma-glutamyl transpeptidase, carbonic anhydrase II, and cytokeratin 19. In contrast, the hepatocyte-like cells colonizing the mesentery showed the phenotype of mature hepatocytes, including an abundant glycogen storage and a lack of alpha-fetoprotein and carbonic anhydrase II expressions. Neither acinar cell nor endocrine differentiation was seen. These findings demonstrate that pancreatic ductal cells can be the progenitor cell for transdifferentiated hepatocytes.
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PMID:Hepatocytic differentiation of cultured rat pancreatic ductal epithelial cells after in vivo implantation. 767 82

To investigate the expression and biological roles of cytokeratin 19 (K19) in development and in adult tissues, we inactivated the mouse K19 gene (Krt1-19) by inserting a bacterial beta-galactosidase gene (lacZ) by homologous recombination in embryonic stem cells, and established germ line mutant mice. Both heterozygous and homozygous mutant mice were viable, fertile, and appeared normal. By 7.5-8.0 days post coitum (dpc), heterozygous mutant embryos expressed lacZ in the notochordal plate and hindgut diverticulum, reflecting the fact that the notochord and the gut endoderm are derived from the axial mesoderm-originated cells. In the adult mutant, lacZ was expressed mainly in epithelial tissues. To investigate the possible functional cooperation and synergy between K19 and K8, we then constructed compound homozygous mutants, whose embryos died approximately 10 dpc. The lethality resulted from defects in the placenta where both K19 and K8 are normally expressed. As early as 9. 5 dpc, the compound mutant placenta had an excessive number of giant trophoblasts, but lacked proper labyrinthine trophoblast or spongiotrophoblast development, which apparently caused flooding of the maternal blood into the embryonic placenta. These results indicate that K19 and K8 cooperate in ensuring the normal development of placental tissues.
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PMID:Cytokeratins 8 and 19 in the mouse placental development. 1106 58

Transplantation of hepatocytes is a promising alternative to liver transplantation for the treatment of severe liver diseases. However, this approach is hampered by the shortage of donor organs and intrinsic limitations of adult hepatocytes. To investigate whether most of the hurdles faced with adult hepatocytes could be surmounted by the use of human fetal hepatoblasts, we have developed a method to isolate, transduce, and cryopreserve hepatoblasts from human livers at an early stage of development (11-13 weeks of gestation). Cells were characterized in vitro for expression of specific markers, and in vivo for their proliferation and differentiation potential after transplantation into athymic mice. Most of the cells (80-90%) harbored a bipotent phenotype, expressing cytokeratins 8/18, albumin, and CK19. They proliferated spontaneously in culture and were efficiently transduced by a beta-galactosidase-expressing retrovirus (90%). After transplantation, cryopreserved cells engrafted into the liver of athymic mice and proliferated, resulting in up to 10% repopulation. Engrafted cells expressed markers of differentiated adult hepatocytes including albumin, alpha1-antitrypsin, cytochrome P450 3A4, and alpha-glutathione-S-transferase. When retrovirally transduced before transplantation they expressed the transgene in vivo. In summary, early human fetal hepatoblasts engraft, proliferate, and mature in athymic mouse liver, without conditioning the donor.
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PMID:Repopulation of athymic mouse liver by cryopreserved early human fetal hepatoblasts. 1568 98