Faculty Research 1990 - 1999
Defective pro alpha 2(I) collagen synthesis in a recessive mutation in mice: a model of human osteogenesis imperfecta.
Animal, Base-Sequence, Bone-and-Bones: pa, Chromosome-Mapping, Collagen: ge, Genes-Recessive, Genes-Structural, Linkage-(Genetics), Mice, Mice-Mutant-Strains, Molecular-Sequence-Data, Mutation, Osteogenesis-Imperfecta: ge, ra, pa, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-NON-P-H-S, SUPPORT-U-S-GOVT-P-H-S
Proc Natl Acad Sci U S A 1993 Mar 1;90(5):1701-5
AR38370/AR/NIAMS, AR39737/AR/NIAMS, AR39870/AR/NIAMS
Osteogenesis imperfecta (OI) is a heritable disorder of connective tissue associated with fractures, osteopenia, and short stature. OI results from mutations affecting the pro alpha 1 or pro alpha 2 gene of type I collagen. We describe a strain of mice with a nonlethal recessively inherited mutation (oim) that results in phenotypic and biochemical features that simulate moderate to severe human OI. The phenotype of homozygous oim mice includes skeletal fractures, limb deformities, generalized osteopenia, and small body size. Their femurs are smaller and demonstrate marked cortical thinning and fewer medullary trabeculae than those of wild-type mice. Breeding studies show the mutation is inherited in most crosses as a single recessive gene on chromosome 6, near the murine Cola-2 gene. Biochemical analysis of skin and bone, as well as isolated dermal fibroblast cultures, demonstrate that alpha 1(I) homotrimeric collagen accumulates in these tissues and is secreted by fibroblasts. Short labeling studies in fibroblasts demonstrate an absence of pro alpha 2(I) collagen chains. Nucleotide sequencing of the cDNA encoding the COOH-propeptide reveals a G deletion at pro alpha 2(I) nucleotide 3983; this results in an alteration of the sequence of the last 48 amino acids. The oim mouse will facilitate the study of type I collagen-related skeletal disease.
Defective pro alpha 2(I) collagen synthesis in a recessive mutation in mice: a model of human osteogenesis imperfecta. Proc Natl Acad Sci U S A 1993 Mar 1;90(5):1701-5