Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused 
by decreased epigenetic repression of the D4Z4 macrosatellite repeats and 
ectopic expression of DUX4, a retrogene encoding a germline transcription factor 
encoded in each repeat. Unaffected individuals generally have more than 10 
repeats arrayed in the subtelomeric region of chromosome 4, whereas the most 
common form of FSHD (FSHD1) is caused by a contraction of the array to fewer 
than 10 repeats, associated with decreased epigenetic repression and variegated 
expression of DUX4 in skeletal muscle. We have generated transgenic mice 
carrying D4Z4 arrays from an FSHD1 allele and from a control allele. These mice 
recapitulate important epigenetic and DUX4 expression attributes seen in 
patients and controls, respectively, including high DUX4 expression levels in 
the germline, (incomplete) epigenetic repression in somatic tissue, and 
FSHD-specific variegated DUX4 expression in sporadic muscle nuclei associated 
with D4Z4 chromatin relaxation. In addition we show that DUX4 is able to 
activate similar functional gene groups in mouse muscle cells as it does in 
human muscle cells. These transgenic mice therefore represent a valuable animal 
model for FSHD and will be a useful resource to study the molecular mechanisms 
underlying FSHD and to test new therapeutic intervention strategies.