Transgenic mouse model of the mild dominant form of osteogenesis imperfecta

Bonadio, Jeffrey; Saunders, Thomas L.; Tsai, Eugene; Goldstein, Steven A.; Morris-Wiman, Joyce; Brinkley, Linda; Dolan, David F.; Altschuler, Richard A.; Hawkins, Jr, Joseph E.; Bateman, John F.; Mascara, Thomas; Jaenisch, Rudolf

Affiliations

¹Howard Hughes Medical Institute, The University of Michigan, Ann Arbor, MI 48109-0650

²Department of Pathology, The University of Michigan, Ann Arbor, MI 48109-0650

³Department of Surgery, The University of Michigan, Ann Arbor, MI 48109-0650

⁴Department of Anatomy and Cell Biology, The University of Michigan, Ann Arbor, MI 48109-0650

⁵Kresge Hearing Research Institute, The University of Michigan, Ann Arbor, MI 48109-0650

⁶Department of Pediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia

⁷Department of Biology, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142

Abstract

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.

Links

DOI: 10.1073/pnas.87.18.7145

PubMed: 2402497

WoS: A1990DZ45300046

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Cited By (24)

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1999	Derwin KA, Soslowsky LJ. A quantitative investigation of structure-function relationships in a tendon fascicle model. J Biomech Eng. December 1999;121(6):598-604.
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2022	Schindeler A, Lee LR, O'Donohue AK, Ginn SL, Munns CF. Curative cell and gene therapy for osteogenesis imperfecta. J Bone Miner Res. May 2022;37(5):826-836.
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