Four unrelated dogs with brittle bones have been identified, each with distinct abnormalities in type I collagen consistent with osteogenesis imperfecta (OI). Three dogs were severely affected and one had moderate disease. Two dogs had dentigenesis imperfecta. The mode of inheritance appeared to be dominant in three dogs and recessive in one dog. During this project, techniques of protein chemistry and cDNA cloning and sequencing will be performed to test the hypothesis that a different mutation in the COL1A1 or COL1A2 gene is the cause of each variant of canine OI. This work will establish the dog as a model of human OI, and permit experimental analyses of the disease that are not possible in humans.
| Campbell, B G; Wootton, J A; Macleod, J N et al. (2001) Canine COL1A2 mutation resulting in C-terminal truncation of pro-alpha2(I) and severe osteogenesis imperfecta. J Bone Miner Res 16:1147-53 |
| Campbell, B G; Wootton, J A; MacLeod, J N et al. (2000) Sequence of normal canine COL1A1 cDNA and identification of a heterozygous alpha1(I) collagen Gly208Ala mutation in a severe case of canine osteogenesis imperfecta. Arch Biochem Biophys 384:37-46 |
| Campbell, B G; Wootton, J A; MacLeod, J N et al. (1998) Sequence of canine COL1A2 cDNA: nucleotide substitutions affecting the cyanogen bromide peptide map of the alpha 2(I) chain. Arch Biochem Biophys 357:67-75 |
