12 research outputs found
Generation of the first autosomal dominant osteopetrosis type II (ADO2) disease models.
Autosomal dominant osteopetrosis type II (ADO2) is a heritable osteosclerotic disorder dependent on osteoclast impairment. In most patients it results from heterozygous missense mutations in the chloride channel 7 (CLCN7) gene, encoding for a 2Cl(-)/1H(+) antiporter. By a knock-in strategy inserting a missense mutation in the Clcn7 gene, our two research groups independently generated mouse models of ADO2 on different genetic backgrounds carrying the homolog of the most frequent heterozygous mutation (p.G213R) in the Clcn7 gene found in humans. Our results demonstrate that the heterozygous model holds true presenting with higher bone mass, increased numbers of poorly resorbing osteoclasts and a lethal phenotype in the homozygous state. Considerable variability is observed in the heterozygous mice according with the mouse background, suggesting that modifier genes could influence the penetrance of the disease gene. (C) 2013 Elsevier Inc. All rights reserved
New Generation Devices for Transcatheter Aortic Valve Implantation
This chapter aims to offer a comprehensive overview of the important challenges still to be faced in terms of actual and possible drawbacks of the existing devices, as well as of the yet unmet clinical and socioeconomical demands. This continuously improving technology is accelerating the path toward a next generation of superior TAVR devices