Linking genotype to phenotype in human FSHD muscle biopsies and mouse muscle expressing DUX4 protein

Investigator: Joel R Chamberlain PhD

Category: Research - Basic

Despite extremely low-level expression of DUX4 in vivo, we have succeeded in identifying DUX4 protein in a human FSHD biopsy and in muscle from an adult mouse model of FSHD.  Preliminary data physically associates DUX4 protein expression and a specific type of damage in both human biopsies and in the muscle of our DUX4 mouse model.  To further investigate DUX4 protein associated effects in FSHD muscle we will obtain additional human biopsies to evaluate the significance of the effects with respect to disease.  Also, DUX4 protein expression in the mouse model implicates an immune response downstream of DUX4 expression that will be investigated.  The proposed aims in this application describe experiments to study the phenotypic effects of DUX4 expression in vivo for a better understanding of the mechanism of DUX4 induced muscle toxicity.  This work will contribute to the growing body of research deciphering disease mechanism and is expected to aid in identifying the best routes for FSHD therapy development.