D4Z4-12.5 mice have a repressed D4Z4 chromatin structure in somatic cells and only express DUX4 at consistently detectable levels in germline tissues while in D4Z4-2.5 mice, there is a partial opening of the chromatin structure similar to FSHD patients and derepression of DUX4 leading to the molecular hall mark of the disease with few nuclei expressing high amounts of DUX4 protein. Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.