Rothnagel J A, Longley M A, Holder R A, Bundman D S, Seki T, Bickenbach J R, Roop D R
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.
J Dermatol Sci. 1994 Jul;7 Suppl:S164-9. doi: 10.1016/0923-1811(94)90047-7.
Recent advances have challenged the prevailing view that keratins are merely passive bystanders of keratinocyte biology. With the exciting discovery that three autosomal dominant genetic skin disorders, epidermolysis bullosa simplex (EBS), epidermolytic hyperkeratosis (EHK) and palmoplantar keratoderma (PPK), are in fact disorders of keratins comes the realization that the integrity of the keratin filament network is crucial to the structural integrity of the skin. Since it has been recently established that mutations in keratins K5/K14, K1/K10 and K9 are causative for these keratinocyte disorders, it is very likely that mutations in K6 or in its obligate partner, K16 will result in disease. In order to test this we have produced transgenic mice that express a mutant K6 gene. These mice develop a progressive scarring alopecia at about 6 months of age. Later, the denuded areas developed a keratosis which was prone to infection. Ultrastructural analysis suggests that hair loss is due to the destruction of the outer root sheath. We believe that these mice are models of another keratin disorder.
最近的进展对一种普遍观点提出了挑战，即角蛋白仅仅是角质形成细胞生物学的被动旁观者。随着令人兴奋的发现，即三种常染色体显性遗传性皮肤病，单纯性大疱性表皮松解症（EBS）、表皮松解性角化过度症（EHK）和掌跖角化病（PPK），实际上是角蛋白疾病，人们意识到角蛋白丝网络的完整性对于皮肤的结构完整性至关重要。由于最近已经确定角蛋白K5/K14、K1/K10和K9中的突变是这些角质形成细胞疾病的病因，很可能K6或其紧密伴侣K16中的突变会导致疾病。为了验证这一点，我们培育了表达突变K6基因的转基因小鼠。这些小鼠在大约6个月大时出现进行性瘢痕性脱发。后来，脱毛区域出现了易于感染的角化病。超微结构分析表明脱发是由于外根鞘的破坏。我们认为这些小鼠是另一种角蛋白疾病的模型。
