Endocrine Abstracts

Osteogenesis imperfecta (OI), the most common among the rare hereditary skeletal dysplasias, is a juvenile form of osteoporosis ranging from mild to perinatal lethal forms. Classical OI is a dominant disease affecting the COL1A1 and COL1A2 genes encoding for the α chains of type I collagen, the most abundant protein of the bone extracellular matrix (ECM). In the last decade new causative genes associated to dominant, recessive and X-linked transmission of the disease and encoding for proteins involved in type I collagen biosynthesis, processing and secretion as well as in osteoblasts differentiation and activity have been described. How mutations in these genes cause the bone fragility phenotype still require further investigation, but already shed new light on bone biology. The molecular basis of OI was historically attributed to the presence of abnormal collagen in the ECM. Nevertheless, mutant collagen is partially retained in the ER and its misfolding and intracellular accumulation had been observed in OI patients’ cells and animal models of classical and new OI forms. A deep understanding of the matrix and intracellular molecular mechanism of the disease as well as the development of new therapeutic approaches for OI and other bone fragility disorders benefit of the use of appropriated animal models. A review of the achievement obtained by the generation and characterization of murine models for dominant and recessive OI forms will be provided. The more recent development and use of teleost models, that provide new tools for osteochondrodysplasia investigation, will be discussed.