Alternative splicing of the human CFTR gene was studied previously and shown not to generate functional CFTR-like chloride ion channels. However, it is possible that some of the alternatively spliced forms may encode CFTR proteins with different functions. The ovine CFTR gene is very similar to the human gene and has regulatory mechanisms in common. To evaluate whether the alternatively spliced forms of human CFTR are conserved in the sheep, the splice forms of the ovine CFTR gene were examined. A transcript lacking exon 9 was observed in the sheep, but unlike the human exon 9-transcript, it did not result from a polymorphic intron 8 splice acceptor site. Sheep CFTR transcripts lacking exon 17b were seen and have also been described in the human. Transcripts lacking 98 bp of the 5' end of exon 13, the whole of exon 13, and both exons 14b and 15 respectively were seen in sheep but have not been reported in human. Splice site donor and acceptor sequences were isolated, and alternative transcripts were shown to result from a combination of aberrant sites and competition of 5' splice donor sequences.
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http://dx.doi.org/10.1007/s00335-003-3013-1 | DOI Listing |
Int J Mol Sci
December 2024
Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/B, 35131 Padova, Italy.
Limb-girdle muscular dystrophy type 2E/R4 (LGMD2E/R4) is a rare disease that currently has no cure. It is caused by defects in the gene, mainly missense mutations, which cause the impairment of the sarcoglycan complex, membrane fragility, and progressive muscle degeneration. Here, we studied the fate of some β-sarcoglycan (β-SG) missense mutants, confirming that, like α-SG missense mutants, they are targeted for degradation through the ubiquitin-proteasome system.
View Article and Find Full Text PDFDrug Dev Ind Pharm
January 2025
School of Medicine, Charles Institute of Dermatology, University College Dublin, Dublin, Ireland.
J Biol Chem
December 2024
Physiology & Biomedical Engineering, Mayo Clinic College of Medicine & Science, Rochester, MN, 55906; Nephrology & Hypertension, Mayo Clinic College of Medicine & Science, Rochester, MN, 55906. Electronic address:
The chloride transporter-channel SLC26A9 is mediated by a reciprocal regulatory mechanism through the interaction between its cytoplasmic STAS domain and the R domain of CFTR. In vertebrate Slc26a9s, the STAS domain structures are interrupted by a disordered loop which is conserved in mammals but is variable in non-mammals. Despite the numerous studies involving the STAS domains in SLC26 proteins, the role of the disordered loop region has not been identified.
View Article and Find Full Text PDFBiomed Rep
February 2025
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
G protein-coupled estrogen receptor 1 (GPER1) plays a crucial role in the progression of breast cancer and has emerged as a promising therapeutic target. However, while missense mutations in GPER1 have been detected in breast invasive carcinoma (BIC) samples, the resulting molecular, cellular and pharmacological changes remain unclear. The present study categorized BIC samples from The Cancer Genome Atlas database based on mutation information available in the cBioPortal database.
View Article and Find Full Text PDFExpert Rev Respir Med
December 2024
Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Introduction: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane regulator (CFTR) gene, leading to progressive lung disease and systemic complications. Lung disease remains the primary cause of morbidity and mortality, making early detection of lung function decline crucial. The Lung Clearance Index (LCI), derived from the multiple breath washout (MBW) test, has emerged as a sensitive measure for identifying early airway disease.
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