Tendon and Motor Phenotypes in the Crtap-/- Mouse Model of Recessive Osteogenesis Imperfecta
Osteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass with bone fragility, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon/ligament dysfunction in OI pathogenesis is largely unknown. Using the Crtap-/- mouse model of severe, recessive OI, we found that mutant Achilles tendons and patellar ligaments were thinner with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar ligaments from Crtap-/- mice also had fewer progenitors with a concomitant increase in immature cells. RNA-seq analysis of Achilles tendons and patellar ligaments from 1-month Crtap-/- mice revealed dysregulation in matrix gene expression concomitant with predicted alterations in TGF-{beta}, inflammatory, and metabolic signaling. Finally, a series of behavioral tests revealed severe motor impairments and reduced grip strength in 4-month Crtap-/- mice - a phenotype that correlates with the tendon/ligament pathology.