Cystic transmembrane regulator gene

Moss, R. B., Rodman, D., Spencer, L. T., Aitken, M. L., Zeitlin, P. L., Waltz, D., Milla, C., Brody, A. S., Clancy, J. P., Ramsey, B., Hamblett, N. and Heald, A. E. (2004). Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs... 

Moss, R.B. et al.. Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis a multicenter, double-blind, placebo-controUed trial. Chest, 125,509,2004. 

The cystic fibrosis (c/) gene was first identified in 1989. It codes for a 170 kDa protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which serves as a chloride channel in epithelial cells. Inheritance of a mutant cftr gene from both parents results in the CF phenotype. While various organs are affected, the most severely affected are the respiratory epithelial cells, which have, unsurprisingly, become the focus of attempts at corrective gene therapy. 

Rosenfeld, M.A., Yoshimura, K., Trapnell, B.C., et al. (1992). In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium. Cell, 68(1), 143-155. 

CaMKI is located in cytoplasm and nuclei and is likely to participate in regulation of gene transcription. In vitro CaMKI phosphorylates substrates such as synapsin and the cystic fibrosis transmembrane regulator although its in vivo substrates are yet to be identified. CaMKI is activated by phosphorylation by CaMKK when both kinases are calcium and CaM bound. The 25-residue CaM-binding peptide of CaMKI forms an o -hehcal stmcture. Two hydrophobic residues are located at positions 1 and 14 (Trp-303 and Met-316). The peptide induces the bending of the central hehx with the interaction of both the N- and C-domains of CaM (pdb 1MXE). > 1... 

Mucoviscidosis or cystic fibrosis (CF) is indeed one of the most common autosomal recessive diseases. It is characterized by the production of a viscous secretion in the excretory glands. Accordingly, pancreatic cystic fibrosis can be observed in the pancreatic area and cylindrical bronchiectases in the pulmonary area. The inspissation of bile and mucus leads to obstruction of the bile canaliculi and subsequently to cholestasis. The gene product is characterized as cystic fibrosis transmembrane regulator (CFTR). (252) The gene defect, which is located on chromosome 7, causes a disorder of the intracellular transport of chloride ions (probably also of chloride ion secretion) and thus triggers the occurrence of CF. The incidence of mucoviscidosis is about 1 2,000-4,500. 

Yoshimura K, Rosenfeld MA, Nakamura H, Scherer EM, Pavirani A, Lecocq JP, Crystal RG. Expression of the human cystic fibrosis transmembrane conductance regulator gene in the mouse lung after in vivo intratracheal plasmid-mediated gene transfer. Nucleic Acids Res 1992, 20, 3233-3240. 

Cystic fibrosis is a hereditary disorder caused by mutation in the cystic fibrosis transmembrane conductance regulator gene that encodes a cyclic adenosine monophosphate-regulated chloride channel. Defects in chloride ion transport in the airway epithelia lead to abnormal airway secretions, impaired mucociliary clearance, chronic bacterial infection, bronchiectasis, and premature death. Delivery of the cystic fibrosis transmembrane conductance regulator cDNA by adenovirus vectors or the plasmid-liposome complex resulted in transient correction of the defects in patients with cystic fibrosis. Formulations of cationic lipid-DNA complexes for aerosol delivery are being explored to improve on the gene therapy approach. 

Yoshimura K, Chu CS, Crystal RG. Alternative splicing of intron 23 of the human cystic fibrosis transmembrane conductance regulator gene resulting in a novel exon and transcript coding for a shortened intracytoplasmic C terminus. J Biol Chem 1993 268 686. 

The primary structure refers to the amino acid sequence of the polypeptide chain. An error caused by a single incorrect amino acid amongst a chain of 1480 amino acids can seriously affect the function of the protein. This happens in people with cystic fibrosis who have a defective CFTR (cystic fibrosis transmembrane conductance regulator) gene, which produces a defective chloride transporter protein. In 70% of people with cystic fibrosis, the mutation is deletion of 3 base pairs in the DNA, which results in the loss of phenylalanine... 

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