1. Characterization of Nasal Potential Difference in cftr Knockout and F508del-CFTR Mice
- Author
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Siradiou Diallo, Delphine Roussel, Isabelle Sermet-Gaudelus, Emilie Saussereau, Laurent Debarbieux, Aleksander Edelman, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Institut Pasteur [Paris] (IP), Cellule Pasteur UPMC, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP), E. Saussereau received a PhD grant from Vaincre la Mucoviscidose (IC0704)., Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris], Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Biologie Moléculaire du Gène chez les Extrêmophiles ( BMGE ), Institut Pasteur [Paris]-Université Pierre et Marie Curie - Paris 6 ( UPMC ), and Debarbieux, Laurent
- Subjects
Male ,Pathology ,Anatomy and Physiology ,Cystic Fibrosis ,Mouse ,lcsh:Medicine ,Cystic Fibrosis Transmembrane Conductance Regulator ,Mucous membrane of nose ,[ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Cystic fibrosis ,MESH: Mice, Knockout ,Membrane Potentials ,Mice ,0302 clinical medicine ,Autosomal Recessive ,F508del cftr ,MESH : Membrane Potentials ,Medicine ,MESH : Female ,MESH: Animals ,lcsh:Science ,MESH: Cystic Fibrosis Transmembrane Conductance Regulator ,Mice, Knockout ,0303 health sciences ,Multidisciplinary ,biology ,Animal Models ,respiratory system ,Cystic fibrosis transmembrane conductance regulator ,MESH: Reproducibility of Results ,Electrophysiology ,030220 oncology & carcinogenesis ,MESH: Nasal Mucosa ,Female ,Research Article ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Cell Physiology ,MESH: Cystic Fibrosis ,Clinical Research Design ,MESH : Male ,03 medical and health sciences ,Model Organisms ,MESH : Cystic Fibrosis ,MESH : Mice ,Genetics ,MESH: Membrane Potentials ,Animals ,Humans ,Animal Models of Disease ,MESH: Mice ,Biology ,030304 developmental biology ,Clinical Genetics ,MESH: Humans ,business.industry ,MESH : Reproducibility of Results ,MESH : Cystic Fibrosis Transmembrane Conductance Regulator ,MESH : Humans ,lcsh:R ,Reproducibility of Results ,Human Genetics ,medicine.disease ,MESH : Disease Models, Animal ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,MESH: Male ,MESH : Nasal Mucosa ,Disease Models, Animal ,Nasal Mucosa ,Potential difference ,biology.protein ,MESH : Mice, Knockout ,lcsh:Q ,MESH : Animals ,Fluid Physiology ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,MESH: Disease Models, Animal ,business ,MESH: Female - Abstract
BACKGROUND:Treatments designed to correct cystic fibrosis transmembrane conductance regulator (CFTR) defects must first be evaluated in preclinical experiments in the mouse model of cystic fibrosis (CF). Mice nasal mucosa mimics the bioelectric defect seen in humans. The use of nasal potential difference (V(TE)) to assess ionic transport is a powerful test evaluating the restoration of CFTR function. Nasal V(TE) in CF mice must be well characterized for correct interpretation., METHODS:We performed V(TE) measurements in large-scale studies of two mouse models of CF--B6;129 cftr knockout and FVB F508del-CFTR--and their respective wild-type (WT) littermates. We assessed the repeatability of the test for cftr knockout mice and defined cutoff points distinguishing between WT and F508del-CFTR mice., RESULTS.We determined the typical V(TE) values for CF and WT mice and demonstrated the existence of residual CFTR activity in F508del-CFTR mice. We characterized intra-animal variability in B6;129 mice and defined the cutoff points for F508del-CFTR chloride secretion rescue. Hyperpolarization of more than -2.15 mV after perfusion with a low-concentration Cl(-) solution was considered to indicate a normal response., CONCLUSIONS: These data will make it possible to interpret changes in nasal V(TE) in mouse models of CF, in future preclinical studies.
- Published
- 2013