Ectopic synthesis of epidermal cytokeratins in pancreatic islet cells of transgenic mice interferes with cytoskeletal order and insulin production

Manfred Blessing, Ulrich Rüther, Werner W. Franke

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The members of the multigene family of intermediate filament (IF) proteins are expressed in various combinations and amounts that are specific for a given pathway or state of differentiation. Previous experiments in which the cell type-specific IF cytoskeleton was altered by introducing foreign IF proteins into cultured cells or certain tissues of transgenic animals have shown a remarkable tolerance, without detectable interference with cell functions. To examine the importance of the cell type-specific cytokeratin (CK) IF pattern, we have studied the ectopic expression of CK genes in different epithelia of transgenic mice. Here we report changes observed in the β cells of pancreatic islets expressing the genes for human epidermal CKs 1 and/or 10 brought under control of the rat insulin promoter. Both genes were efficiently expressed, resulting in the appearance of numerous and massive bundles of aggregated IFs, resembling those of epidermal keratinocytes. While the synthesis of epidermal CK 10 was readily accommodated and compatible with cell function, mice expressing CK 1 in their cells, alone or in combination with CK 10, developed a special form of diabetes characterized by a drastic reduction of insulin-secretory vesicles and of insulin-and CK 1-producing cells. In many CK 1-producing cells, accumulations of fibrous or granular material containing CK 1 were also seen in the nucleus. This demonstration of functional importance of the specific CK-complement in an epithelial cell indicates a contribution of cell type-specific factors to cytoplasmic IF compartmentalization and that the specific CK complement can be crucial for functions and longevity of a given kind of epithelium.

Original languageEnglish (US)
Pages (from-to)743-755
Number of pages13
JournalJournal of Cell Biology
Volume120
Issue number3
DOIs
StatePublished - Feb 1993

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Keratins
Islets of Langerhans
Transgenic Mice
Insulin
Intermediate Filaments
Intermediate Filament Proteins
Cytoskeleton
Epithelium
Genetically Modified Animals
Secretory Vesicles
Multigene Family
Keratinocytes
Genes
Cultured Cells
Epithelial Cells

ASJC Scopus subject areas

  • Cell Biology

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Ectopic synthesis of epidermal cytokeratins in pancreatic islet cells of transgenic mice interferes with cytoskeletal order and insulin production. / Blessing, Manfred; Rüther, Ulrich; Franke, Werner W.

In: Journal of Cell Biology, Vol. 120, No. 3, 02.1993, p. 743-755.

Research output: Contribution to journalArticle

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