Since DUX4 is toxic, animal model development has been challenging, but progress has been made, revealing that tight regulation of DUX4 expression is critical for creating viable animals that develop myopathy.
The degenerative muscle disorder facioscapulohumeral dystrophy (FSHD) is thought to be caused by the inappropriate expression of the Double Homeobox 4 (Dux4) protein in muscle cells leading to apoptosis.
DUX4 constitutes a major candidate pathogenic protein for facioscapulohumeral muscular dystrophy (FSHD), the third most common form of inherited myopathy.
These results establish that DUX4-fl expression per se is not sufficient for FSHD muscle pathology and indicate that quantitative modifiers of DUX4-fl expression and/or function and family genetic background are determinants of FSHD muscle disease progression.