Genome-wide chromatin accessibility and transcriptome profiling show minimal epigenome changes and coordinated transcriptional dysregulation of hedgehog signaling in Danforth's short tail mice.

Danforth's short tail (Sd) mice provide an excellent model for investigating the underlying etiology of human caudal birth defects, which affect 1 in 10 000 live births. Sd animals exhibit aberrant axial skeleton, urogenital and gastrointestinal development similar to human caudal malformation syndromes including urorectal septum malformation, caudal regression, vertebral-anal-cardiac-tracheo-esophageal fistula-renal-limb (VACTERL) association and persistent cloaca. Previous studies have shown that the Sd mutation results from an endogenous retroviral (ERV) insertion upstream of the Ptf1a gene resulting in its ectopic expression at E9.