Disease relevance of CFTR

• Hemolysin B is a member of the so-called ATP binding cassette transporter superfamily, which includes the multidrug resistance P-glycoprotein, the cystic fibrosis CFTR protein, and the major histocompatibility complex-associated transporter of antigenic peptides [1].
• Because lung disease is by far the greatest cause of mortality among people with cystic fibrosis, it is important to determine how loss of CFTR function causes lung disease [2].
• It is caused by a functional absence or deficiency of the cystic fibrosis transmembrane conductance regulator and manifests in the gut as meconium ileus [3].

Psychiatry related information on CFTR

• CFTR is known to be more abundant in the airway epithelium during the second trimester of human development than after birth [4].

High impact information on CFTR

• Alternatively it might reflect an additional role for CFTR in the developing airway epithelium [4].
• These results support a role for CFTR in differentiation of the respiratory epithelium and suggest that its expression levels are not merely reflecting major changes in the sodium/chloride bulk flow close to term [4].
• We evaluated CFTR expression using a quantitative assay of mRNA at 14 time points through gestation and showed highest levels at the start of the second trimester followed by a gradual decline through to term [4].
• The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a small conductance chloride ion channel that may interact directly with other channels including the epithelial sodium channel (ENaC) [4].
• Using a percutaneous ultrasound-guided injection technique, we have clearly demonstrated proof of principle for substantial transgene delivery to the fetal airways providing levels of gene expression that could be relevant for a therapeutic application of CFTR expressing vectors [5].

Chemical compound and disease context of CFTR

• Cystic fibrosis transmembrane conductance regulator's (CFTR) best understood function is as an anion channel, but increasing attention has been given to its role in HCO(3)(-) transport [2].

Biological context of CFTR

• The variant is a guanine to adenine base change at position 1019 of the ovine CFTR cDNA, corresponding to an arginine (R) to glutamine (Q) amino acid substitution at position 297 in the predicted CFTR polypeptide [6].
• Alternative splicing of the ovine CFTR gene [7].
• Nine regions of the ovine CFTR gene were screened, corresponding to human CFTR gene exons 4, 6b, 7, 9, 10, 11, 12, 17b and 20 [8].
• CFTR, chloride concentration and cell volume: could mammalian protein histidine phosphorylation play a latent role [9]?
• Linkage analysis confirmed the location of CFTR on sheep chromosome 4 [10].

Anatomical context of CFTR

• Based on these observations, it is reasonable to hypothesize that the NBFs from the CFTR are associated with the plasma membrane and have extracellularly-accessible regions [11].
• Ovine male genital duct epithelial cells differentiate in vitro and express functional CFTR and ENaC [12].
• This interpretation is supported by RT-PCR data showing that vas deferens and epididymis cells express CFTR and ENaC mRNA [12].
• These findings suggest that cultured ovine vas deferens and epididymis cells absorb Na(+) via amiloride-sensitive epithelial Na(+) channels (ENaC) and secrete Cl(-) and HCO(-)(3) via apical cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels [12].

Associations of CFTR with chemical compounds

• CFTR is highly expressed in serous cells of submucosal glands and the Calu-3 serous cell model secretes HCO(3)(-) [2].
• CFTR is a cyclic AMP-regulated epithelial Cl(-) channel, and appears to control the activity of several other transport proteins [13].

Analytical, diagnostic and therapeutic context of CFTR

• Northern blot analysis and reverse transcription-PCR have shown that the patterns of expression of the ovine CFTR gene are very similar to those seen in humans [14].
• Temporal regulation of CFTR expression during ovine lung development: implications for CF gene therapy [4].
• Comparative genomic sequence analysis of ovine and human CFTR identified high levels of homology between the core elements in several potential regulatory elements defined as DNase I hypersensitive sites in human CFTR [15].

References