Lessons from keratin 18 knockout mice: formation of novel keratin filaments, secondary loss of keratin 7 and accumulation of liver-specific keratin 8-positive aggregates.
Lessons from keratin 18 knockout mice: formation of novel keratin filaments, secondary loss of keratin 7 and accumulation of liver-specific keratin 8-positive aggregates.
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角蛋白18基因敲除小鼠的经验教训：新型角蛋白丝的形成，角蛋白7的继发性损失以及肝特异性角蛋白8阳性聚集体的积累。
DOI：
10.1083/jcb.140.6.1441
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发表时间：
1998-03-23
影响因子：
7.8
通讯作者：
Melton, DW
中科院分区：
文献类型：
--
作者：
Magin, TM;Schröder, R;Leitgeb, S;Wanninger, F;Zatloukal, K;Grund, C;Melton, DW
在这里，我们报告角蛋白18无效小鼠的分析。与K8的消融不同，K8与K18一起在胚胎和简单的成年上皮细胞中表达，K18缺失小鼠是存活的，可生育的，并显示出正常的寿命。在年轻的K18基因敲除小鼠中，肝细胞完全没有角蛋白丝。然而，典型的桥粒形成和维持。然而，老年K18基因敲除小鼠出现了独特的肝脏病理学，其中异常肝细胞含有K8阳性聚集体。这些细胞对泛素和MM 120 -1染色呈阳性，被鉴定为马洛里小体，这是人类酒精性肝炎的标志之一。这是第一次证明，一个角蛋白的消融导致其单一伴侣的积累。另一个惊人的发现是K7在几种组织中的缺失或急剧下调，尽管它正在转录。此外，K18基因敲除小鼠揭示了无尾K19体内致突变形成能力的新见解。由于K7的意外继发性丢失，在K18缺失小鼠的子宫上皮中仅表达K8/19。该组织的免疫电子显微镜显示存在典型的K8/19 IF，从而在体内突出显示K19是K8的完全胜任的伴侣。
Here, we report on the analysis of keratin 18 null mice. Unlike the ablation of K8, which together with K18 is expressed in embryonic and simple adult epithelia, K18 null mice are viable, fertile, and show a normal lifespan. In young K18 null mice, hepatocytes were completely devoid of keratin filaments. Nevertheless, typical desmosomes were formed and maintained. Old K18 null mice, however, developed a distinctive liver pathology with abnormal hepatocytes containing K8-positive aggregates. These stained positively for ubiquitin and MM120-1 and were identified as Mallory bodies, one hallmark of human alcoholic hepatitis. This is the first demonstration that the ablation of one keratin leads to the accumulation of its single partner. Another striking finding was the absence or drastic down regulation of K7 in several tissues despite its ongoing transcription. Moreover, K18 null mice revealed new insights in the filament-forming capacity of the tail-less K19 in vivo. Due to the unexpected secondary loss of K7, only K8/19 are expressed in the uterine epithelium of K18 null mice. Immunoelectron microscopy of this tissue demonstrated the presence of typical K8/19 IF, thus highlighting in vivo that K19 is a fully competent partner for K8.
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影响因子：
11.4
作者：
BADER, BL;MAGIN, TM;FRANKE, WW
通讯作者：
FRANKE, WW
影响因子：
7.8
作者：
ALBERS, K;FUCHS, E
通讯作者：
FUCHS, E
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
影响因子：
7.8
作者：
ALBERS, K;FUCHS, E
通讯作者：
FUCHS, E
影响因子：
7.8
作者：
BLESSING, M;RUTHER, U;FRANKE, WW
通讯作者：
FRANKE, WW