BPAG2和相关疾病GABEB基因突变的研究

BPAG2是大疱性类天疱疮的抗原之一，与多种获得性大疱病的发病有关。现发现GABEB一种忍煨越唤缧源箴灞砥に尚钢⒌姆⒉∮肫浠蛉毕萦泄亍１臼匝榻芯抗谑桌鼼ABEB的BPAG2基因突变位点，阐明该突变导致表皮真皮连接受损的发病机理；结合GABEB特征性临床表现迟发性萎缩性秃发，探讨BPAG2分子与毛囊发育的关系，以期在国际上首先发现GABEB患者迟发性萎缩性秃发的发病机理。.

BPAG2 is one of the antigens in auto-immune disease─bullous pemphigoid, and related to a few acquired bullous diseases. Generalized atrophic benign epidermolysis bullosa (GABEB) is a subtype of non-lethal variant of junctional epidermolysis bullosa, with characteristics of generalized blisters, skin atrophy and alopecia. Now mutations in COL17A1, which codes the BPAG2 protein, have been reported to respect to the disease. A few of GABEB patients have mutations in LAMB3, which codes the laminin 5.We have delineated a novel mutation and a new SNP in the first Chinese family with GABEB. The proband investigated in this study, is a homozygote for a missense mutation S265C in COL17A1. The S265C mutation found in our patient is the second mutation located in the intracellular part of BPAG2, which located at the highly conservative region in the evolution of BPAG2.BPAG2 distributes widely and is the main component of hemi-desmosome.One characteristics of GABEB is alopecia, which take place in the childhood not just after birth. To date, little information about BPAG2 in the physiology of hair follicle has been reported. In mouse and rat skin, absence of BPAG staining around developing hair bulbs was found. In adult human follicles, absence of BPAG staining was restricted to the papilla-epithelial interfaces during anagen phase..If BPAG2 expression is heterogeneous during hair cycles, it may have physiological functions in hair cycles, for example, in cell-matrix interactions. We examined the distribution of BPAG2 and COL17A1 mRNA in follicles at different stages of hair cycle in human and mouse. In contrary to the reports mentioned above, we could not find the heterogeneous expression of COL17A1 gene at different stages of follicle cycle both in human and mouse. Like other basement membrane components, such as laminin 5, BPAG2 expression remained constant in the entire hair cycles. It seems likely that BPAG2 molecules functions as a structural protein for the maintaining of follicular integrity rather than a regulatory factor on bulb cell differentiation and hair growth.The result points out the direction for further research on this aspect. We should study the relationship between structure protein and hair cycles and mechanism of alopecia.