IAP insertion in the murine LamB3 gene results in junctional epidermolysis bullosa
IAP insertion in the murine LamB3 gene results in junctional epidermolysis bullosa
复制标题
DOI：
10.1007/s003359900535
复制
发表时间：
1997-09-01
期刊：
影响因子：
2.5
通讯作者：
Swiatek, PJ
中科院分区：
文献类型：
--
作者：
Kuster, JE;Guarnieri, MH;Swiatek, PJ
层粘连蛋白-5分子在各种上皮细胞与基底膜的附着中起作用。层粘连蛋白-5编码基因的突变与Herlitz交界性大疱性表皮松解症(HJEB)有关，HJEB是一种严重的、通常是致命的人类水泡病。在这里，我们报告了一个自发性突变的常染色体隐性遗传水泡病小鼠的特征。这些小鼠表现为皮肤和粘膜表面上皮下水泡和异常的半桥粒，缺乏亚基下致密板。通过连锁分析，该基因缺陷被定位在远端染色体(Chr)1上一个2 cM的区域，该区域先前定位了层粘连蛋白5亚单位基因LnmB3。Northern印迹分析和免疫组织化学方法均未检测到LnmB3mRNA和LN-5蛋白的表达。DNA序列分析表明，LnmB3基因缺陷是由于在外显子/内含子连接处插入A颗粒(LAP)导致编码序列中断所致。这些发现提示了层粘连蛋白-5在半桥粒形成中的作用，并表明LamB3(IAP)突变是一种有用的HJEB小鼠模型。
The laminin-5 molecule functions in the attachment of various epithelia to basement membranes. Mutations in the laminin-5-coding genes have been associated with Herlitz junctional epidermolysis bullosa (HJEB), a severe and often lethal blistering disease of humans. Here we report the characterization of a spontaneous mouse mutant with an autosomal recessive blistering disease. These mice exhibit sub-epithelial blisters of the skin and mucosal surfaces and abnormal hemidesmosomes lacking sub-basal dense plates. By linkage analysis the genetic defect was localized to a 2-cM region on distal Chromosome (Chr) 1 where a laminin-5 subunit gene, LnmB3, was previously localized. LnmB3 mRNA and laminin-5 protein were undetectable by Northern blot analysis and immunohistochemical methods, respectively. DNA sequence analysis indicated that the LnmB3 genetic defect resulted from disruption of the coding sequence by insertion of an intracisternal-A particle (LAP) at an exon/intron junction. These findings suggest a role for laminin-5 in hemidesmosome formation and indicate that the LamB3(IAP) mutant is a useful mouse model for HJEB.