Out of balance: consequences of a partial keratin 10 knockout.
Out of balance: consequences of a partial keratin 10 knockout.
复制标题
失去平衡：部分角蛋白 10 敲除的后果。
作者：
Julia Reichelt;Christoph Bauer;Rebecca M. Porter;E. Lane;Volker Herzog;T. M. Magin
最近，我们产生了角蛋白10基因敲除小鼠，这为显性遗传性皮肤病表皮角化过度症提供了一个有价值的模型。在这里，我们调查了他们的表型的分子基础。杂合子和纯合子表达截短的角蛋白10肽，已被确定直接通过微测序。角蛋白10 T的单克隆抗体的表位映射使我们能够研究其相对于角蛋白6的分布，角蛋白6在角蛋白10敲除小鼠中高度表达，通过双免疫金电子显微镜。这表明角蛋白10 T仅限于与角蛋白1的复合物，但不与角蛋白6混合。后者不与角蛋白16/17形成延伸的细丝，而是聚集体。角蛋白6/16不能补偿正常角蛋白1/10细丝的缺乏。值得注意的是，角蛋白6聚集体与透明角质颗粒严格共定位。残余角蛋白1/10 T团块位于细胞周边和维持正常结构的桥粒处。令人惊讶的是，角蛋白2 e，一种专门用于承受机械应力的角蛋白，在纯合子角蛋白10敲除小鼠的脚掌表皮中完全丢失，这表明角蛋白10是它的伴侣。角蛋白10 T的选择性配对和角蛋白2 e的丢失表明，体内角蛋白比体外角蛋白更不混杂。角蛋白10基因敲除小鼠和表皮角化过度症中的皮肤脆性可能是两种互补机制的结果，即正常角蛋白1/10细丝的减少和角蛋白6/16的增加，具有较差的粘附形成能力。
Recently we generated keratin 10 knockout mice which provided a valuable model for the dominantly inherited skin disorder epidermolytic hyperkeratosis. Here we investigated the molecular basis for their phenotype. Hetero- and homozygotes expressed a truncated keratin 10 peptide which has been identified directly by microsequencing. Epitope mapping of monoclonal antibodies to keratin 10T enabled us to study its distribution relative to keratin 6, which is highly expressed in keratin 10 knockout mice, by double-immunogold electron microscopy. This revealed that keratin 10T was restricted to complexes with keratin 1 but did not mix with keratin 6. The latter did not form extended filaments with keratins 16/17 but aggregates. Keratins 6/16 were unable to compensate for the lack of normal keratin 1/10 filaments. Remarkably keratin 6 aggregates strictly colocalized with keratohyalin granules. Residual keratin 1/10T clumps were located in the cell periphery and at desmosomes which maintained a normal architecture. Surprisingly keratin 2e, a keratin tailored to sustain mechanical stress, was completely lost in paw sole epidermis of homozygous keratin 10 knockout mice, pointing to keratin 10 as its partner. The selective pairing of keratin 10T and the loss of keratin 2e indicate that in vivo keratins are less promiscuous than in vitro. Skin fragility in keratin 10 knockout mice and in epidermolytic hyperkeratosis is probably the consequence of two complementing mechanisms namely a decrease of normal keratin 1/10 filaments and an increase in keratins 6/16 with a poor filament-forming capacity.
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DOI：
10.1073/pnas.94.3.849
发表时间：
1997-02-04
影响因子：
11.1
作者：
Maniotis, AJ;Chen, CS;Ingber, DE
通讯作者：
Ingber, DE
皮肤病转基因模型。
影响因子：
--
作者：
Rothnagel,JA;Greenhalgh,DA;Wang,XJ;Sellheyer,K;Bickenbach,JR;Dominey,AM;Roop,DR
通讯作者：
Roop,DR
具有诱导性皮肤起泡疾病表型的转基因小鼠模型。
DOI：
10.1073/pnas.93.25.14776
发表时间：
1996
影响因子：
11.1
作者：
Takahashi,K;Coulombe,PA
通讯作者：
Coulombe,PA
影响因子：
56.9
作者：
CHEN, BM;GRINNELL, AD
通讯作者：
GRINNELL, AD