화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.373, No.1, 113-118, 2008
Mild processing defect of porcine Delta F508-CFTR suggests that Delta F508 pigs may not develop cystic fibrosis disease
Recent efforts have made significant progress in generating transgenic pigs with the Delta F508-CFFR mutation to model the lung and pancreatic disease of human cystic fibrosis. However, species differences in the processing and function of human, pig and mouse Delta F508-CFTR reported recently raise concerns about the phenotypic consequence of the gene-targeted pig model. The purpose of the present study was to characterize the Delta F508 mutant of porcine CFTR to evaluate the severity of its processing defect. Biochemical and immunofluorescence analysis in transfected COS7 and FRT cells indicated that pig Delta F508-CFTR efficiently targets to the plasma membrane and is present mainly as the mature glycosylated protein. Functional characterization in stably transfected FRT cells by fluorometric and electrophysiological assays supported efficient plasma membrane targeting of pig Delta F508-CFTR. The mild cellular processing defect of pig Delta F508-CFFR suggests that its gene-targeted pig model may not develop the lung and pancreatic phenotypes seen in CF patients. (C) 2008 Elsevier Inc. All rights reserved.