Transgenic mouse model of the mild dominant form of osteogenesis imperfecta.
Osteogenesis imperfecta type I is a mild, dominantly inherited, connective tissue disorder characterized by bone fragility. Mutations in type I collagen account for all known cases. In Mov-13 mice, integration of a murine retrovirus within the first intron of the alpha 1(I) collagen gene results in a null allele blocked at the level of transcription. This study demonstrates that mutant mice heterozygous for the null allele are a model of osteogenesis imperfecta type I. A defect in type I collagen production is associated with dominant-acting morphological and functional defects in mineralized and nonmineralized connective tissue and with progressive hearing loss. The model provides an opportunity to investigate the effect of a reduced amount of type I collagen on the structure and integrity of extracellular matrix. It also may represent a system in which therapeutic strategies to strengthen connective tissue can be developed.
Bonadio
J
J
Howard Hughes Medical Institute, Department of Pathology, University of Michigan, Ann Arbor 48109-0650.
Saunders
T L
TL
Tsai
E
E
Goldstein
S A
SA
Morris-Wiman
J
J
Brinkley
L
L
Dolan
D F
DF
Altschuler
R A
RA
Hawkins
J E
JE
Bateman
J F
JF
D000818:Animals; D001933:Brain Stem / Q000503:physiopathology; D002460:Cell Line; D003094:Collagen / Q000032:analysis / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D005072:Evoked Potentials, Auditory; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D012016:Reference Values; D012867:Skin / Q000032:analysis / Q000473:pathology
C000716128:Col1a1 protein, mouse; D000090602:Collagen Type I, alpha 1 Chain; D003094:Collagen