mineralization are not clear. However, it has been 
suggested that the abnormal radiographic appear- 
ance results from an inability of bones deficient in 
organic matrix and mineral to resist skeletal muscle 
activity in utero. 
The elastic modulus of bone is a composite of 
the material properties of its mineral and organic 
phases. An extracellular matrix defect (i.e., a defect 
within the organic phase of bone) primarily is re- 
sponsible for skeletal fragility in OI-II patients. All 
OI-II cases to date have been associated with struc- 
tural mutations in genes encoding the constituent 
a-chains of type I collagen, the most abundant pro- 
tein in bone. These mutations alter the function of 
type I collagen by disrupting the conformation of 
molecules that incorporate mutant a-chains. 
For some time it has been argued that a change 
in collagen conformation logically would affect 
mineralization. The collagen molecule exists in tis- 
sues as a fibril. The collagen fibril is a heteropoly- 
mer in which collagen molecules are packed in a 
highly ordered, staggered, three-dimensional array. 
A series of gaps between molecules are created 
that serve as sites of mineral (largely calcium 
PUBLICATIONS 
hydroxyapatite) deposition. A change in collagen 
conformation could disrupt fibril architecture and 
interfere with biomineralization. Experimental evi- 
dence demonstrating abnormal fibrils within the 
OI-II extracellular matrix is noteworthy in this 
regard. 
The laboratory has endeavored to establish a 
model system to study systematically the effects of 
OI-II mutations on biomineralization. A novel 
method to isolate, purify, and propagate dl6 chick 
embryo calvarial cells in cell culture has been de- 
veloped. The cultured cells elaborate and mineral- 
ize a type I collagen-based extracellular matrix. The 
cells are transiently transfectable at rates compara- 
ble to primary dl6 chick embryo tendon cells. In 
addition, a full-length chick a 1(1) cDNA has been 
isolated. The model system should allow an analy- 
sis of the relationship between collagen conforma- 
tion, fibril formation, and mineral deposition by the 
expression of mutagenized cDNAs in osteoblast 
cells. 
Dr. Bonadio is also Assistant Professor of Pathol- 
ogy at the University of Michigan Medical School. 
Books and Chapters of Books 
Byers, P.H., and Bonadio, J. 1989. Collagen: Biochemistry, Biotechnology, and Molecular Biology (Olsen, 
B.R., and Nimmi, M., Eds.). Boca Raton, FL: CRC, vol 4. 
Article 
Patterson, E., Smiley, E., and Bonadio, J. 1989. RNA sequence analysis of a perinatal lethal osteogenesis im- 
perfecta mutation. J Biol Chem 264:10083-10087. 
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