Collagen V haploinsufficiency in a murine model of classic Ehlers–Danlos syndrome is associated with deficient structural and mechanical healing in tendons


Jessica M. Johnston, Brianne K. Connizzo, Snehal S. Shetye, Kelsey A. Robinson, Julianne Huegel, Ashley B. Rodriguez, Mei Sun, Sheila M. Adams, David E. Birk, Louis J. Soslowsky


Classic Ehlers–Danlos syndrome (EDS) patients suffer from connective tissue hyperelasticity, joint instability, skin hyperextensibility, tissue fragility, and poor wound healing due to heterozygous mutations in COL5a1 or COL5a2 genes. This study investigated the roles of collagen V in establishing structure and function in uninjured patellar tendons as well as in the injury response using a Col5a1+/− mouse, a model for classic EDS. These analyses were done comparing tendons from a classic EDS model (Col5a1+/−) with wild-type controls. Tendons were subjected to mechanical testing, histological, and fibril analysis before injury as well as 3 and 6 weeks after injury. We found that Col5a1+/− tendons demonstrated diminished recovery of mechanical competency after injury as compared to normal wild-type tendons, which recovered their pre-injury values by 6 weeks post injury. Additionally, the Col5a1+/−tendons demonstrated altered fibril morphology and diameter distributions compared to the wild-type tendons. This study indicates that collagen V plays an important role in regulating collagen fibrillogenesis and the associated recovery of mechanical integrity in tendons after injury. In addition, the dysregulation with decreased collagen V expression in EDS is associated with a diminished injury response. The results presented herein have the potential to direct future targeted therapeutics for classic EDS patients.