1,721,095 research outputs found
Shedding Light on Bone Morphogenetic Protein (BMP) Signaling Modifiers to Modulate Fibrodysplasia Ossificans Progressiva Severity
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Cleavage of collagen RNA transcripts by hammerhead ribozymes in vitro is mutation-specific and shows competitive binding effects.
No full textOsteogenesis imperfecta
No full textOsteogenesis imperfecta is a phenotypically and molecularly heterogeneous group of inherited connective tissue disorders that share similar skeletal abnormalities causing bone fragility and deformity. Previously, the disorder was thought to be an autosomal dominant bone dysplasia caused by defects in type I collagen, but in the past 10 years discoveries of novel (mainly recessive) causative genes have lent support to a predominantly collagen-related pathophysiology and have contributed to an improved understanding of normal bone development. Defects in proteins with very different functions, ranging from structural to enzymatic and from intracellular transport to chaperones, have been described in patients with osteogenesis imperfecta. Knowledge of the specific molecular basis of each form of the disorder will advance clinical diagnosis and potentially stimulate targeted therapeutic approaches. In this Seminar, together with diagnosis, management, and treatment, we describe the defects causing osteogenesis imperfecta and their mechanism and interrelations, and classify them into five groups on the basis of the metabolic pathway compromised, specifically those related to collagen synthesis, structure, and processing; post-translational modification; folding and cross-linking; mineralisation; and osteoblast differentiation
Alternative splicing in COL1A1 mRNA leads to a partial null allele and two in-frame forms with structural defects in non-lethal osteogenesis imperfecta.
No full textUse of the Cre/Lox recombination system to develop a non-lethal knock-in murine model for osteogenesis imperfecta with an alpha1(I) G349C substitution. Variability in phenotype in BrtlIV mice.
No full textEditorial: molecular mechanisms of heritable connective tissue disorders
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Selective retention and degradation of molecules with a single mutant alpha1(I) chain in the Brtl IV mouse model of OI
No full textExtracellular matrix deposition in cultured dermal fibroblasts from four probands affected by osteogenesis imperfecta.
No full textType I procollagen biosynthesis and matrix deposition were studied in cultured fibroblasts of four probands affected by Osteogenesis Imperfecta and in whom the mutations have been characterized. The mutations along the triple helix altered all biochemical parameters considered, i.e. thermal stability, kinetics of procollagen secretion and rate of maturation from procollagen to collagen. The biochemical findings were peculiar for each case considered, but there was no correlation between biochemical parameters and clinical phenotype. In all our probands, regardless of the clinical severity, mutant chains appeared in the insoluble matrix formed by fibroblasts cultured in the presence of dextran sulfate. The densitometric scanning revealed a relative increased amount of fibronectin, suggesting that the matrix contained a lower quantity of type I collagen. Furthermore, the amount of mutant chains found in the insoluble fraction was clearly less than expected, considering that 75% of new synthesized trimers are abnormal. Therefore, in the presence of a mutation, the protein available for extracellular matrix formation is reduced and the mutant trimers incorporated in the matrix probably interfere with normal fibril performance. The abnormal fibril morphology has a dramatic effect in bone, interfering presumably with a correct mineral deposition and interactions with non/collagenous bone proteins
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