Bonadio J, Saunders T L, Tsai E, Goldstein S A, Morris-Wiman J, Brinkley L, Dolan D F, Altschuler R A, Hawkins J E, Bateman J F
Howard Hughes Medical Institute, Department of Pathology, University of Michigan, Ann Arbor 48109-0650.
Proc Natl Acad Sci U S A. 1990 Sep;87(18):7145-9. doi: 10.1073/pnas.87.18.7145.
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.
I型成骨不全症是一种轻度的、显性遗传的结缔组织疾病，其特征为骨质脆弱。所有已知病例均由I型胶原蛋白的突变引起。在Mov-13小鼠中，一种鼠类逆转录病毒整合到α1(I)胶原蛋白基因的第一个内含子内，导致一个无效等位基因在转录水平受阻。本研究表明，该无效等位基因的杂合突变小鼠是I型成骨不全症的模型。I型胶原蛋白产生缺陷与矿化和非矿化结缔组织中显性作用的形态和功能缺陷以及进行性听力丧失有关。该模型为研究I型胶原蛋白含量减少对细胞外基质结构和完整性的影响提供了机会。它也可能代表一个可以开发强化结缔组织治疗策略的系统。
