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T Magin

Publications and source records attributed to T Magin.

5 recordsLinked to original sources
PubMed2000

Unique and shared functions of different connexins in mice.

BACKGROUND: Connexins are the protein subunits of intercellular gap junction channels. In mammals, they are encoded by a family of at least 15 genes, which show cell-type-specific but overlapping patterns of expression. Mice lacking connexin43 (Cx43) die postnatally from obstruction of the right ventricular outflow tract of the heart. To discriminate between the unique and shared functions of Cx43, Cx40 and Cx32, we generated two 'knock-in' mouse lines, Cx43KI32 and Cx43KI40, in which the coding region of the Cx43 gene was replaced, respectively, by the coding regions of Cx32 or Cx40. RESULTS: Heterozygous mutants were fertile and co-expressed the wild-type and the corresponding recombinant allele in all tissues analyzed. Heterozygous Cx43KI32, but not Cx43KI40, mutant mothers were unable to nourish their pups to weaning age, possibly reflecting a defect in milk ejection. Homozygous mutant males were sterile because of extensive germ-cell deficiency. The ovaries of homozygous Cx43KI32 neonates exhibited all stages of follicular development and ovulation. The hearts of homozygous Cx43KI32 neonates showed mild morphological defects, but the cardiac morphology of homozygous Cx43KI40 neonates was relatively normal. Spontaneous ventricular arrhythmias were observed in most Cx43KI40 and some Cx43KI32 mutant mice, suggesting increased ventricular vulnerability in these mice. CONCLUSIONS: The postnatal lethality of Cx43-deficient mice was rescued in Cx43KI32 or Cx43KI40 mice, indicating that Cx43, Cx40 and Cx32 share at least some vital functions. On the other hand, Cx43KI32 and Cx43KI40 mice differed functionally and morphologically from each other and from wild-type mice. Thus, these connexins also have unique functions.

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PubMed2000

Simple epithelial keratins are dispensable for cytoprotection in two pancreatitis models.

Pancreatic acinar cells express keratins 8 and 18 (K8/18), which form cytoplasmic filament (CF) and apicolateral filament (ALF) pools. Hepatocyte K8/18 CF provide important protection from environmental stresses, but disruption of acinar cell CF has no significant impact. We asked whether acinar cell ALF are important in providing cytoprotective roles by studying keratin filaments in pancreata of K8- and K18-null mice. K8-null pancreas lacks both keratin pools, but K18-null pancreas lacks only CF. Mouse but not human acinar cells also express apicolateral keratin 19 (K19), which explains the presence of apicolateral keratins in K18-null pancreas. K8- and K18-null pancreata are histologically normal, and their acini respond similarly to stimulated secretion, although K8-null acini viability is reduced. Absence of total filaments (K8-null) or CF (K18-null) does not increase susceptibility to pancreatitis induced by caerulein or a choline-deficient diet. In normal and K18-null acini, K19 is upregulated after caerulein injury and, unexpectedly, forms CF. As in hepatocytes, acinar injury is also associated with keratin hyperphosphorylation. Hence, K19 forms ALF in mouse acinar cells and helps define two distinct ALF and CF pools. On injury, K19 forms CF that revert to ALF after healing. Acinar keratins appear to be dispensable for cytoprotection, in contrast to hepatocyte keratins, despite similar hyperphosphorylation patterns after injury.

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PubMed2000

Loss- and gain-of-function mutations show a polycomb group function for Ring1A in mice.

The products of the Polycomb group (PcG) of genes act as transcriptional repressors involved in the maintenance of homeotic gene expression patterns throughout development, from flies to mice. Biochemical and molecular evidence suggests that the mouse Ring1A gene is a member of the PcG of genes. However, genetic evidence is needed to establish PcG function for Ring1A, since contrary to all other murine PcG genes, there is no known Drosophila PcG gene encoding a homolog of the Ring1A protein. To study Ring1A function we have generated a mouse line lacking Ring1A and mouse lines overexpressing Ring1A. Both Ring1A(-/-)and Ring1A(+/-) mice show anterior transformations and other abnormalities of the axial skeleton, which indicates an unusual sensitivity of axial skeleton patterning to Ring1A gene dosage. Ectopic expression of Ring1A also results in dose-dependent anterior transformations of vertebral identity, many of which, interestingly, are shared by Ring1A(-/-) mice. In contrast, the alterations of Hox gene expression observed in both type of mutant mice are subtle and involve a reduced number of Hox genes. Taken together, these results provide genetic evidence for a PcG function of the mouse Ring1A gene.

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PubMedDate not supplied

Cessation of cytokeratin expression in a rat hepatoma cell line lacking differentiated functions.

Intermediate-sized filaments (IF) of diameter 7-11 nm occur in the cytoplasm of most cells of vertebrates and their constituent proteins are abundant in most cell types. Expression of IF proteins depends on the route of cell differentiation and five major subclasses of IF proteins have been distinguished: of these, cytokeratins are typical of epithelial cells whereas vimentin occurs in mesenchymally derived cells and some other non-epithelial cells. When epithelial cells are grown in culture this restriction of IF expression is often lost and they begin to synthesize vimentin in addition to cytokeratin, although examples of maintenance of the cell-type-specific expression of only cytokeratin have also been reported. No IFs have been detected in mammalian germ cells or in pre-morula stages of mouse embryogenesis, and the first IF proteins identified in murine blastocysts are cytokeratins of trophectodermal cells. We report here that a dedifferentiated rat hepatoma cell clone, which has become resistant to the action of the glucocorticoid hormone analogue dexamethasone and has lost various liver-specific functions, also stops all synthesis of IF proteins, without obvious consequences for growth and proliferation. The existence of such cells devoid of IF supports the notion that such filaments are not involved in basic cellular functions necessary for growth and proliferation but are related to special functions of the differentiated cell.

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