Fig. 1

Transgene map and FSHD-like model generation. a The synthesized FLExDUX4 (FLExD) transgene, flanked by heterologous lox sites (loxP and lox511), was inserted in the antisense orientation to the Rosa26 promoter and maintains the intron/exon structure and cis mRNA regulatory features, including the PAS and DAE, of the human chromosome 4q35 DUX4 gene. When crossed with ACTA1-MCM mice, the bi-transgenic offspring have the capacity for dosage-dependent, TMX-inducible unidirectional recombination of the transgene, resulting in DUX4 expression exclusively in skeletal muscle and transcribed from the Rosa26 promoter, processed, and terminated in exon 3 using the DUX4 PAS. b Genomic PCR indicating percent transgene recombination in different muscles from FLExD/+ mice and bi-transgenic ACTA1-MCM;FLExD mice with no TMX or 3 days after a single IP injection of 5 mg/kg TMX (low), or two IP injections of 10 mg/kg TMX (high). TA, tibialis anterior; Sol, soleus; GA, gastrocnemius; Qua, quadriceps; Diaph, diaphragm