1. ¹Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
2. ²The Jackson Laboratory, Bar Harbor, Maine, USA
3. ³Department of Dermatology, Medical University of Vienna, Vienna, Austria
4. ⁴Department of Dermatology, Baylor College of Medicine, Houston, Texas, USA

Correspondence: Dr Dennis R. Roop, Department of Dermatology and Regenerative Medicine and Stem Cell Biology Program, University of Colorado at Denver Health Sciences Center, PO Box 6511, Mail Stop 8320, Aurora, Colorado 80045, USA. E-mail: Dennis.Roop@UCHSC.edu

⁵Current address: Department of Dermatology and Regenerative Medicine and Stem Cell Biology Program, University of Colorado at Denver and Health Sciences Center, Aurora, Coloardo 80045, USA

Received 7 May 2007; Accepted 24 June 2007; Published online 13 September 2007.

Abstract

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.