Takahashi K, Yan B, Yamanishi K, Imamura S, Coulombe P A
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA.
Genomics. 1998 Oct 15;53(2):170-83. doi: 10.1006/geno.1998.5476.
The type II keratin 6 (K6) features a complex expression pattern, with a constitutive component in a subset of stratified epithelia and an inducible component following injury and other types of acute challenges. Multiple genes encoding highly related K6 isoforms have been described for human and bovine, a unique feature among mammalian keratin genes. Here we report on the cloning and characterization of two functional genes and their cDNAs encoding the K6 isoforms in mouse and two related pseudogenes. A systematic comparison of the mouse and human K6 genes suggests that they evolved independently after these species diverged. The mK6alpha and mK6beta genes are organized in tandem with the same transcriptional orientation in the mouse genome. Similar to the human isoforms, the coding sequences for mK6alpha and mK6beta isoforms show approximately 95% identity. The two mouse K6 genes are differentially regulated at the mRNA level in several stratified epithelia. The mK6alpha isoform mRNA clearly predominates in intact trunk skin of adult mice, where it is restricted to the outer root sheath of hair follicles. Both mRNAs are induced in epidermis and proximal hair follicles as early as 1 h following acute injury or topical application of phorbol esters and subsequently increase to a comparable extent but with different kinetics. These novel findings have important implications for the evolution, regulation, and function of K6 genes in mammalian species.
II型角蛋白6（K6）具有复杂的表达模式，在一部分复层上皮中呈组成型表达，在损伤及其他类型的急性刺激后呈诱导型表达。在人和牛中已发现多个编码高度相关K6异构体的基因，这在哺乳动物角蛋白基因中是一个独特的特征。在此，我们报告了小鼠中两个功能性基因及其编码K6异构体的cDNA以及两个相关假基因的克隆和特征。对小鼠和人类K6基因的系统比较表明，它们在这些物种分化后独立进化。mK6α和mK6β基因在小鼠基因组中以相同的转录方向串联排列。与人类异构体相似，mK6α和mK6β异构体的编码序列显示出约95%的同一性。在几种复层上皮中，两个小鼠K6基因在mRNA水平上受到不同的调控。mK6α异构体mRNA在成年小鼠完整的躯干皮肤中明显占主导地位，在那里它仅限于毛囊的外根鞘。在急性损伤或局部应用佛波酯后1小时内，两种mRNA在表皮和近端毛囊中均被诱导，随后以相似的程度增加，但动力学不同。这些新发现对哺乳动物物种中K6基因的进化、调控和功能具有重要意义。
