The disease is caused by a COL1A missense mutation in the SERPINH1 gene, a gene known to be involved in collagen maturation, similar to the human condition. The maturation and correct folding of collagens is a complicated process involving a large number of accessory proteins and chaperones. Two proteins are involved in the 3-hydroxylation of a specific proline residue in collagen I. One represents the enzymatically active prolyl-3-hydroxylase 1 and the other called cartilage-associated protein which forms a complex with the prolyl-3-hydroxylase. Separate genes are thought to be involved in these processes.
Collagen I is the most abundant protein in the human body and its highly ordered fibril structure is responsible for its special mechanical properties. Together with inorganic hydroxylapatite it is the main component of bones and gives them elasticity while the hydroxylapatite alone would be very brittle. Defects in the structure of the highly ordered collagen I triple helix lead to osteogenesis imperfecta
A number of dog breeds are predisposed including the Dachshund, Golden Retriever, Beagle, Collie, Poodle, Norwegian Elkhound and Bedlington Terrier. In Golden Retrievers a COL1A1 mutation and in Beagles a COL1A2 mutation has been reported to cause osteogenesis imperfecta. For other canine OI cases the underlying genetic defect has not been elucidated.
Clinical signs include joint pain, spontaneous bone and teeth fractures, joint hyperlaxity, and reduced bone density on radiography. Primary teeth are usually extremely thin-walled and brittle. Blood tests usually reveal severe osteopenia characterized by impairment of lamellar bone formation in the long bones, skull, and vertebral column.
Histological examination of bone samples is usually unrewarding in terms of pathology.
DNA testing is currently available for definitive diagnosis of this condition.
There is no definitive therapy for this condition.
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