Mutations in prolyl 3-hydroxylase 1 (P3H1), encoded by the human LEPRE1 gene (leprecan 1 or leucine proline-enriched proteoglycan 1), have been associated with recessive Osteogenesis Imperfecta (OI).
This strain carries H662A (histidine to alanine) mutation in a catalytic site of the mouse Lepre1 gene. Expression of protein in bone does not appear to be affected, but enzymatic activity of P3H1 is abolished. The protein retains the ability to form a complex with cartilage associated protein (CRTAP) and thus its collagen chaperone function, however. These mice have a normal appearance, have no growth defects, have normal cartilage plate histology, and normal cortical bone, but show decreased trabecular bone. This model recapitulates elements of the bone phenotype of OI, but not the cartilage and growth phenotypes caused by the loss of the prolyl 3-hydroxylation complex.
