ECTOPIC SYNTHESIS OF EPIDERMAL CYTOKERATINS IN PANCREATIC-ISLET CELLS OF TRANSGENIC MICE INTERFERES WITH CYTOSKELETAL ORDER AND INSULIN PRODUCTION
ECTOPIC SYNTHESIS OF EPIDERMAL CYTOKERATINS IN PANCREATIC-ISLET CELLS OF TRANSGENIC MICE INTERFERES WITH CYTOSKELETAL ORDER AND INSULIN PRODUCTION
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DOI：
10.1083/jcb.120.3.743
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发表时间：
1993-02-01
影响因子：
7.8
通讯作者：
FRANKE, WW
中科院分区：
文献类型：
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作者：
BLESSING, M;RUTHER, U;FRANKE, WW
中间丝（IF）蛋白的多基因家族的成员以特定于给定途径或分化状态的各种组合和量表达。以前的实验中，细胞类型特异性IF细胞骨架被引入外源IF蛋白到培养的细胞或转基因动物的某些组织中改变，已经显示出显着的耐受性，没有可检测到的干扰细胞功能。为了研究细胞类型特异性细胞角蛋白（CK）IF模式的重要性，我们研究了CK基因在转基因小鼠不同上皮细胞中的异位表达。在这里，我们报告观察到的变化，胰岛β细胞表达人类表皮细胞角蛋白1和/或10的基因的控制下，大鼠胰岛素启动子。这两种基因都有效表达，导致出现大量和大量的聚集的IF束，类似于表皮角质形成细胞。虽然表皮CK 10的合成很容易调节，并与细胞功能相容，但在β细胞中表达CK 1的小鼠，单独或与CK 10组合，发展成一种特殊形式的糖尿病，其特征是胰岛素分泌囊泡和胰岛素和CK 1产生细胞的急剧减少。在许多产生CK 1的细胞中，细胞核中也可见含有CK 1的纤维状或颗粒状物质的积聚。上皮细胞中特异性CK-补体的功能重要性的这一证明表明细胞类型特异性因子对细胞质IF区室化的贡献，并且特异性CK补体对于给定种类的上皮的功能和寿命可能是至关重要的。
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 beta 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 beta 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.