To evaluate both whether SHN3 inhibition is a potential therapeutic approach to treat OI and also whether SHN3-mediated regulation of the skeletal vascular microenvironment is relevant to OI phenotypes, we intercrossed Shn3−/− mice with Col1a2oim/oim mice.14 Ablation of SHN319,31 provided a complete or near complete reversal of the low bone mass observed in both trabecular and cortical bone compartments in both male and female Col1a2oim/oim mice (Figs. 4a–c and S7). This evidence concerns the gene HIVEP3 and osteogenesis imperfecta.