The secreted carbonic anhydrase (CA VI) is believed to be one of the oldest mammalian CAs in evolutionary terms. To elucidate its gene structure and compare it with other members of the alpha-CA family, we cloned genomic fragments encoding the bovine CA6 gene and determined its exon/intron organization. The gene spans approx. 25 kb and consists of eight exons and seven introns. Exon 1 encodes t...

Osteogenesis imperfecta (OI) is a spectrum of genetic disorders characterized by bone fragility. It is caused by dominant mutations affecting the synthesis and/or structure of type I procollagen or by recessively inherited mutations in genes responsible for the posttranslational processing/trafficking of type I procollagen. Recessive OI type VI is unique among OI types in that it is characteriz...

Mutations in myosin VI (Myo6) cause deafness and vestibular dysfunction in Snell's waltzer mice. Mutations in two other unconventional myosins cause deafness in both humans and mice, making myosin VI an attractive candidate for human deafness. In this report, we re®ned the map position of human myosin VI (MYO6) by radiation hybrid mapping and characterized the genomic structure of myosin VI. Hu...

Particulate hexavalent chromium ((Cr(VI)) compounds are human lung carcinogens. These compounds induce DNA damage, chromosome aberrations, and concentration-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between Cr(VI)-induced DNA damage and chromosome aberrations is poorly understood. Accordingly, this study focused on examining the role of Ku80, a gene i...

Chromium (Cr) is a widespread environmental contaminant and a known human carcinogen. We have used shuttle vector systems in yeast, mammalian cells, and transgenic mice to characterize the mutational specificity and premutational DNA damage induced by Cr(VI) and its reduction intermediates in order to elucidate the mechanism by which Cr induces mutations. In the yeast system, treatment of vecto...

OBJECTIVES The purpose of this study was to test the hypothesis that cardiac-directed expression of adenylyl cyclase VI (AC(VI)) facilitates atrioventricular (AV) nodal conduction. BACKGROUND Cardiac-directed expression of AC(VI), unlike other strategies to increase cyclic adenosine monophosphate generation, reduces mortality in murine cardiomyopathy. Recent reports suggest that AC(VI) expres...

Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1(-/-)) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between...

Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Inhibition of Cr(VI)-induced carcinogenesis by a dietary antioxidant is a novel approach. Quercetin is one of the most abundant dietary flavonoids widely present in many fruits and vegetables, possesses potent antioxidant and anticancer properties. MicroRNA-21 (miR-21) is a key onco...

ehlers-danlos syndrome (eds vi)(omim 225400) is an autosomal recessive disease of the connective tissue. it is characterized by severe hypotonia at birth, progressive kyphoscoliosis, skin hyperelasticity, joint hypermobility, microcornea, rupture of arteries and eye globe, and osteopenia. collagen lysyl hydroxylase is deficient in these patients. deficiency of the activity of lysyl hydroxylase,...