Collectively, engineering the sheep ALPL missense-mutation (c.1077 C > G) model of HPP accurately recapitulated many of the varied clinical manifestations observed in individuals with HPP34, satisfying the most stringent criteria for an animal model for the study of human musculoskeletal disease and marking a major advance beyond the existing and largely limited murine models. The gene discussed is ALPL; the disease is musculoskeletal system disorder.