Mice expressing a mutant desmosomal cadherin exhibit abnormalities in desmosomes, proliferation, and epidermal differentiation.
Mice expressing a mutant desmosomal cadherin exhibit abnormalities in desmosomes, proliferation, and epidermal differentiation.
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表达突变桥粒钙粘蛋白的小鼠表现出桥粒、增殖和表皮分化的异常。
DOI：
10.1083/jcb.133.6.1367
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发表时间：
1996-06
影响因子：
7.8
通讯作者：
Fuchs, E
中科院分区：
文献类型：
--
作者：
Allen, E;Yu, QC;Fuchs, E
桥粒蛋白是钙粘附素超家族的成员，构成桥粒的核心。体外研究表明，桥粒蛋白的胞质结构域与蛋白结合；然而，关于该结构域在体内桥粒识别或组装中的作用，以及桥粒蛋白突变与表皮分化和疾病的可能关系，人们知之甚少。为了解决这些问题，我们使用转基因小鼠技术在已知表达野生型桥粒蛋白的细胞中产生了NH2末端截短的桥粒蛋白(天疱疮寻常型抗原或Dsg3)。在2天内，新生的转基因动物表现出爪子肿胀，背部剥落，尾尖变黑。在组织学和超微结构分析中，爪部和尾部细胞间隙的增宽和桥粒的破坏尤其明显。桥粒数量显著减少，体积较小，结构通常特殊。免疫荧光和免疫电子显微镜显示半桥粒成分定位无明显异常，但桥粒成分组织异常，导致斑块内超微结构丢失。在桥粒丢失普遍但仍有粘连结构的区域，表皮增厚，棘层和角质层明显增加，颗粒层厚度变化，部分区域角化不全。有趣的是，细胞增殖的急剧增加也伴随着生化变化，包括已知与过度增殖相关的整合素表达的变化。在一些皮肤区域也检测到炎症反应。总而言之，这些发现表明，桥粒芯糖蛋白的突变可以扰乱表皮细胞与细胞之间的黏附，引发皮肤的一系列变化。
Desmogleins are members of the cadherin superfamily which form the core of desmosomes. In vitro studies indicate that the cytoplasmic domain of desmogleins associates with plakoglobin; however, little is known about the role of this domain in desmosome recognition or assembly in vivo, or about the possible relation of desmoglein mutations to epidermal differentiation and disease. To address these questions we used transgenic mouse technology to produce an NH2-terminally truncated desmoglein (Pemphigus Vulgaris Antigen or Dsg3) in cells known to express its wild-type counterpart. Within 2 d, newborn transgenic animals displayed swelling of their paws, flakiness on their back, and blackening of the tail tip. When analyzed histologically and ultrastructurally, widening of intercellular spaces and disruption of desmosomes were especially striking in the paws and tail. Desmosomes were reduced dramatically in number and were smaller and often peculiar in structure. Immunofluorescence and immunoelectron microscopy revealed no major abnormalities in localization of hemidesmosomal components, but desmosomal components organized aberrantly, resulting in a loss of ultrastructure within the plaque. In regions where desmosome loss was prevalent but where some adhesive structures persisted, the epidermis was thickened, with a marked increase in spinous and stratum corneum layers, variability in granular layer thickness, and parakeratosis in some regions. Intriguingly, a dramatic increase in cell proliferation was also observed concomitant with biochemical changes, including alterations in integrin expression, known to be associated with hyperproliferation. An inflammatory response was also detected in some skin regions. Collectively, these findings demonstrate that a mutation in a desmoglein can perturb epidermal cell-cell adhesion, triggering a cascade of changes in the skin.
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影响因子：
7.8
作者：
Ozawa, M;Kemler, R
通讯作者：
Kemler, R
DOI：
10.1016/s0190-9622(94)70059-1
发表时间：
1994-04-01
影响因子：
13.8
作者：
NICKOLOFF, BJ;NAIDU, Y
通讯作者：
NAIDU, Y
影响因子：
64.5
作者：
AMAGAI, M;KLAUSKOVTUN, V;STANLEY, JR
通讯作者：
STANLEY, JR
影响因子：
3.3
作者：
FUJIMORI, T;TAKEICHI, M
通讯作者：
TAKEICHI, M
MDCK上皮细胞中脱骨组装的调节：质膜上膜核和细胞质斑块结构域的配位。
影响因子：
7.8
作者：
Pasdar, M;Krzeminski, K A;Nelson, W J
通讯作者：
Nelson, W J