Whitbread L A, Powell B C
John Curtin School of Medical Research, Australian National University, Acton, ACT, 0200, Australia.
Exp Cell Res. 1998 Nov 1;244(2):448-59. doi: 10.1006/excr.1998.4217.
The intermediate filament keratin, K15, is present in variable abundance in stratified epithelia. In this study we have isolated and characterized the sheep K15 gene, focusing on its expression in the follicles of sheep and mice. We show that K15 is expressed throughout the hair cycle in the basal layer of the outer root sheath that envelops the follicle. Strikingly, however, in large medullated wool follicles, a small group of basal outer root sheath cells located in the region thought to contain hair follicle stem cells are K15-negative. In the follicle bulb K15 is expressed in cells situated next to the dermal papilla but not in the inner bulb cells. Elsewhere, K15 is expressed at a low, variable level in the basal layer of the epidermis and sebaceous gland, often in a punctate pattern. In the esophagus of the sheep K15 expression is restricted to the basal layer, in contrast to human esophagus where it is expressed throughout the epithelium. Transgenic mouse lines established with a 15-kb sheep K15 gene construct exhibited faithful expression and showed no phenotypic consequences of K15 overexpression. An investigation of transgene expression showed that K15 is continuously expressed in outer root sheath cells during the hair cycle. Given its expression in the mitotically active basal cell layers of diverse epithelia and the follicle, K15 expression appears to signal an early stage in the pathway of keratinocyte differentiation that precedes the decision of a cell to become epidermal or hair-like.
中间丝角蛋白K15在复层上皮中的丰度各不相同。在本研究中，我们分离并鉴定了绵羊K15基因，重点研究其在绵羊和小鼠毛囊中的表达。我们发现，K15在包围毛囊的外根鞘基底层的整个毛发生长周期中均有表达。然而，引人注目的是，在大型有髓毛毛囊中，位于被认为含有毛囊干细胞区域的一小群外根鞘基底细胞是K15阴性的。在毛囊球部，K15在紧邻真皮乳头的细胞中表达，但在内球细胞中不表达。在其他部位，K15在表皮和皮脂腺的基底层中低水平、不定量地表达，通常呈点状分布。与人类食管中K15在整个上皮中均有表达不同，在绵羊食管中K15的表达仅限于基底层。用15kb的绵羊K15基因构建体建立的转基因小鼠品系表现出忠实的表达，且未显示K15过表达的表型后果。对转基因表达的研究表明，在毛发生长周期中，K15在外根鞘细胞中持续表达。鉴于其在多种上皮和毛囊有丝分裂活跃的基底细胞层中的表达，K15的表达似乎标志着角质形成细胞分化途径中一个早期阶段，该阶段早于细胞决定成为表皮细胞或毛样细胞的阶段。
