Deletion of the codon encoding the phenylalanine residue at position 508（ΔF508） in the cystic fibrosis transmembrane conductance regulator（CFTR） is the most common mutation causing cystic fibrosis（CF）.The human...Deletion of the codon encoding the phenylalanine residue at position 508（ΔF508） in the cystic fibrosis transmembrane conductance regulator（CFTR） is the most common mutation causing cystic fibrosis（CF）.The human ΔF508 mutation results in a CFTR protein with impaired folding,trafficking,and gating in human and rodents.Recent studies suggest that pig ΔF508-CFTR can be efficiently processed to the plasma membrane as maturely glycosylated protein,indicating species difference of the molecular mechanisms of CFTR cellular maturation.In this study,the functional characterization in stably transfected FRT cells cultured at 37 ℃ demonstrates that pig ΔF508-CFTR is remarkably more sensitive to specific CFTR inhibitors CFTRinh-172 and GlyH101 than wildtype pig CFTR.The wildtype pig CFTR is more sensitive to GlyH101 than to CFTRinh-172.The present study indicates that the gating property of ΔF508-CFTR chloride channel is altered and GlyH101 may be a more suitable small molecule probe for generating CF phenotypes in pig tissues.展开更多
Background: Aquagenic wrinkling of the palms (AWP) is a rare condition characterized by the rapid and transient formation of edematous whitish plaques on the palms on exposure to water (the so- called hand- in- the- b...Background: Aquagenic wrinkling of the palms (AWP) is a rare condition characterized by the rapid and transient formation of edematous whitish plaques on the palms on exposure to water (the so- called hand- in- the- bucket sign). The changes may be asymptomatic or accompanied by pruritic or burning sensations. First described in 1974 in patients with cystic fibrosis- and still primarily reported in these patients- this condition has been previously described only in females. Specific mutations in CFTR, the gene responsible for cystic fibrosis, have not been reported previously in patients with AWP. Observations: We describe 2 patients with AWP, both of whom are homozygous for the △ F508 mutation in CFTR: a 17- year- old boy- the first male reported to have this condition- who has had AWP for 3 years and a 13- year- old girl who has had AWP for 6 months. Conclusions: Cystic fibrosis should be considered in patients with AWP, and patients with cystic fibrosis should be asked about symptoms of this condition. Although the etiology of AWP is unknown, the association with cystic fibrosis, and with marasmus and cyclooxygenase- 2 inhibitors, suggests that exposure of the skin to abnormally high concentrations of salt may play a role in its pathogenesis.展开更多
基金Supported by the General Administration of Quality Supervision,Inspection and Quarantine of China(No.2006IK145)the Natural Science Foundation of Jilin Province,China(Nos.200705269 and 20030708)+1 种基金the Natural Science Foundation of Changchun City,China(No.2007sf19)the Science and Technology Fund from the Education Department of Liaoning Province,China(No.20060492)
文摘Deletion of the codon encoding the phenylalanine residue at position 508（ΔF508） in the cystic fibrosis transmembrane conductance regulator（CFTR） is the most common mutation causing cystic fibrosis（CF）.The human ΔF508 mutation results in a CFTR protein with impaired folding,trafficking,and gating in human and rodents.Recent studies suggest that pig ΔF508-CFTR can be efficiently processed to the plasma membrane as maturely glycosylated protein,indicating species difference of the molecular mechanisms of CFTR cellular maturation.In this study,the functional characterization in stably transfected FRT cells cultured at 37 ℃ demonstrates that pig ΔF508-CFTR is remarkably more sensitive to specific CFTR inhibitors CFTRinh-172 and GlyH101 than wildtype pig CFTR.The wildtype pig CFTR is more sensitive to GlyH101 than to CFTRinh-172.The present study indicates that the gating property of ΔF508-CFTR chloride channel is altered and GlyH101 may be a more suitable small molecule probe for generating CF phenotypes in pig tissues.
文摘Background: Aquagenic wrinkling of the palms (AWP) is a rare condition characterized by the rapid and transient formation of edematous whitish plaques on the palms on exposure to water (the so- called hand- in- the- bucket sign). The changes may be asymptomatic or accompanied by pruritic or burning sensations. First described in 1974 in patients with cystic fibrosis- and still primarily reported in these patients- this condition has been previously described only in females. Specific mutations in CFTR, the gene responsible for cystic fibrosis, have not been reported previously in patients with AWP. Observations: We describe 2 patients with AWP, both of whom are homozygous for the △ F508 mutation in CFTR: a 17- year- old boy- the first male reported to have this condition- who has had AWP for 3 years and a 13- year- old girl who has had AWP for 6 months. Conclusions: Cystic fibrosis should be considered in patients with AWP, and patients with cystic fibrosis should be asked about symptoms of this condition. Although the etiology of AWP is unknown, the association with cystic fibrosis, and with marasmus and cyclooxygenase- 2 inhibitors, suggests that exposure of the skin to abnormally high concentrations of salt may play a role in its pathogenesis.
