Mice expressing a mutant Krt75 (K6hf) allele develop hair and nail defects resembling pachyonychia congenita
Mice expressing a mutant Krt75 (K6hf) allele develop hair and nail defects resembling pachyonychia congenita
复制标题
DOI：
10.1038/sj.jid.5701038
复制
发表时间：
2008-02-01
影响因子：
6.5
通讯作者：
Roop, Dennis R.
中科院分区：
文献类型：
--
作者：
Chen, Jiang;Jaeger, Karin;Roop, Dennis R.
KRT 75（以前称为K6 hf）是角蛋白6（KRT 6）家族的同种型之一，位于人类12号染色体和小鼠15号染色体上的II型细胞角蛋白基因簇内。KRT 75在毛囊的伴发层和上生发基质区、毛干的髓质和甲床的上皮中表达。KRT 6家族成员中的显性突变，例如KRT 6A和KRT 6 B中的显性突变分别引起先天性甲肥厚（PC）-1和-2。为了确定KRT 75在皮肤附件中的功能，我们将显性突变引入Krt 75的螺旋起始肽中的高度保守残基中。表达这种突变形式的Krt 75的小鼠出现类似PC的毛发和指甲缺陷。该小鼠模型提供了Krt 75在维持毛干和指甲完整性中所起的关键作用的体内证据。此外，在我们的突变Krt 75小鼠中观察到的表型表明，KRT 75可能是筛选在KRT 6A、KRT 6 B、KRT 16或KRT 17中没有表现出明显突变的PC患者的候选基因，特别是那些具有广泛毛发受累的PC患者。
KRT75 (formerly known as K6hf) is one of the isoforms of the keratin 6 (KRT6) family located within the type II cytokeratin gene cluster on chromosome 12 of humans and chromosome 15 of mice. KRT75 is expressed in the companion layer and upper germinative matrix region of the hair follicle, the medulla of the hair shaft, and in epithelia of the nail bed. Dominant mutations in members of the KRT6 family, such as in KRT6A and KRT6B cause pachyonychia congenita (PC)-1 and -2, respectively. To determine the function of KRT75 in skin appendages, we introduced a dominant mutation into a highly conserved residue in the helix initiation peptide of Krt75. Mice expressing this mutant form of Krt75 developed hair and nail defects resembling PC. This mouse model provides in vivo evidence for the critical roles played by Krt75 in maintaining hair shaft and nail integrity. Furthermore, the phenotypes observed in our mutant Krt75 mice suggest that KRT75 may be a candidate gene for screening PC patients who do not exhibit obvious mutations in KRT6A, KRT6B, KRT16, or KRT17, especially those with extensive hair involvement.