Awarded a one-year, $100,000 grant from Pachyonychia Congenita Project.
To thoroughly understand pachyonychia congenita, this disease ought to be studied in models. A mouse models was recently generated. It offers the opportunity to investigate pachyonychia congenita at the cell and molecular levels. Knowledge gained from this investigation is valuable for guiding the development of novel therapies.
Project Title: Defining molecular mechanisms underlying hyperkeratosis of pachyonychia congenita in a mouse model
expressing a mutant of Krt6a
Principal Investigator (PI) Name: Jiang Chen, MD
PI Affiliations: Department of Dermatology, Stony Brook University
Abstract
Genetically engineered mouse models capable of recapitulating diseases at genetic and phenotypic levels are valuable for the understanding of disease mechanisms. They can also be used as platforms for testing novel therapies. A mutation was recently introduced into the Krt6a gene. This mutation is homologous to a frequently reported mutation in pachyonychia congenita (PC) patients. Consistent with patients, heterozygous mutant mice exhibited early signs of PC. We postulate that this mouse model is an ideal model to investigate the mechanisms underlying PC and to test
promising therapeutic strategies. In this research, molecular pathways underlying the development of PC phenotypes will be investigated in mutant mice, and a novel gene-correction approach will be tested in mutant epidermal keratinocytes. Outcomes from this research may provide important insight into future development of systemic and
personalized treatment for PC.
