Abnormal alpha 2-chain in type I collagen from a patient with a form of osteogenesis imperfecta.

P H Byers; J R Shapiro; D W Rowe; K E David; K A Holbrook

doi:10.1172/JCI110815

Abnormal alpha 2-chain in type I collagen from a patient with a form of osteogenesis imperfecta.

P H Byers, J R Shapiro, D W Rowe, K E David, and K A Holbrook

Published March 1, 1983 - More info

View PDF

Abstract

Dermal fibroblasts in culture from a woman with a mild to moderate form of osteogenesis imperfecta synthesize two species of the pro alpha 2-chain of type I procollagen. One chain is normal. The abnormal chain has a slightly faster mobility than normal during electrophoresis in sodium dodecyl sulfate polyacrylamide gels. Analysis of cyanogen bromide peptides of the pro alpha-chain, the alpha-chain, and of the mammalian collagenase cleavage products of the pro alpha- and alpha-chains indicates that the abnormality is confined to the alpha 2(I)CB4 fragment and is consistent with loss of a short triple-helical segment. Type I collagen production was decreased, perhaps because the molecules that contained the abnormal chain were unstable, with a resultant alteration in the ratio of type III to type I collagen secreted into culture medium. Collagen fibrils in bone and skin had a normal periodicity but their diameters were 50% of control; the bone matrix was undermineralized. The structural abnormality in the alpha 2(I)-chain in this patient may affect molecular stability, intermolecular interactions, and collagen-mineral relationships that act to decrease the collagen content of tissues and affect the mineralization of bone.

Images.