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| 1 | Characterization of two rat models of cystic fibrosis—KO and F508del CFTR—Generated by Crispr-Cas9显示文摘Background: Genetically engineered animals are essential for gaining a proper understanding of the disease mechanisms of cystic fibrosis(CF). The rat is a relevant laboratory model for CF because of its zootechnical capacity, size, and airway characteristics, including the presence of submucosal glands.Methods: We describe the generation of a CF rat model(F508 del) homozygous for the p.Phe508 del mutation in the transmembrane conductance regulator(Cftr) gene. This model was compared to new Cftr-/-rats(CFTR KO). Target organs in CF were examined by histological staining of tissue sections and tooth enamel was quantified by micro-computed tomography. The activity of CFTR was evaluated by nasal potential difference(NPD) and short-circuit current measurements. The effect of VX-809 and VX-770 was analyzed on nasal epithelial primary cell cultures from F508 del rats.Results: Both newborn F508 del and Knock out(KO) animals developed intestinal obstruction that could be partly compensated by special diet combined with an osmotic laxative. The two rat models exhibited CF phenotypic anomalies such as vas deferens agenesis and tooth enamel defects. Histology of the intestine, pancreas, liver, and lungs was normal. Absence of CFTR function in KO rats was confirmed ex vivo by short-circuit current measurements on colon mucosae and in vivo by NPD, whereas residual CFTR activity was observed in F508 del rats. Exposure of F508 del CFTR nasal primary cultures to a combination of VX-809 and VX-770 improved CFTR-mediated Cl-transport.Conclusions: The F508 del rats reproduce the phenotypes observed in CFTR KO animals and represent a novel resource to advance the development of CF therapeutics. | Elise Dreano Marc Bacchetta Juliette Simonin Louise Galmiche Claire Usal Lotfi Slimani Jérémy Sadoine Laurent Tesson Ignacio Anegon Jean-Paul Concordet Aurélie Hatton Lucile Vignaud Danielle Tondelier Isabelle Sermet-Gaudelus Marc Chanson Charles-Henry Cottart | 2019 | Animal Models and Experimental Medicine2019，2，4： | 3 |
| 2 | Postischemic treatment by trans-resveratrol in rat liver ischemia-reperfusion:a possible strategy in liver surgery显示文摘 | Hassan-Khabbar S Cottart CH Wendum D | | 0，，04： | 1 |
| 3 | Protective effect ofpost-ischemic treatment with trans-resveratrol on cytokineproduction and neutrophil recruitment by rat liver 显示文摘 | Hassan-Khabbar S Vamy M Cottart CH et at | 2010 | Biochimie2010，92，4： | 1 |
| 4 | Hepatoprotective effect of endogenous nitric oxide during ischemia-reperfusion in the rat显示文摘 | Cottart CH Do L Blanc MC | 1999 | Hepatology1999，29，3： | 1 |
| 5 | Resveratrol bioavailability and toxicity in humans显示文摘 | Cottart C H V Nivet-Antoine | 2010 | Mol Nutr Food Res2010，54，1： | 1 |
| 6 | Review of recent data on the metabolism,biological effects,and toxicity of resveratrolin humans显示文摘 | Cottart CH Nivet-Antoine V Beaudeux JL | 2014 | Mol Nutr Food Res2014，58，1： | 1 |
| 7 | Hepatoprotective effect of nitric oxide during ischemia-reperfusion in the rat显示文摘 | Cottart CH Do L Blanc MC | 1999 | Hepatology1999，29，3： | 1 |
| 8 | Protective effect of post-ischemic treatment with trans-resveratrol on cytokine production and neutrophil recruitment by rat liver显示文摘 | Hassan-Khabbar S Vamy M Cottart CH | | 0，，04： | 1 |
| 9 | Resveratrol bioavailability and toxicity in humans显示文摘 | Cottart CH Nivet-Antoine V Laguillier-Morizot C | | 0，，01： | 1 |
| 10 | Hepatoprotective effect of endogenous nitric oxide during Ischemia-Reperfusion in the rat显示文摘 | Cottart C H Do L Blanc M C | | 0，，： | 1 |
| 11 | trans -Resveratrol downregulates Txnip overexpression occurring during liver ischemia-reperfusion显示文摘 | Valérie Nivet-Antoine Charles-Henry Cottart Hervé Lemaréchal Michel Vamy Isabelle Margaill Jean-Louis Beaudeux Dominique Bonnefont-Rousselot Didier Borderie | 2010 | Biochimie2010，，12： | 1 |
| 12 | Catalase rs769214 SNP in elderly malnutrition and during renutri- tion: is glucagon to blame显示文摘 | Hebert - Schuster M Cottart CH Laguillier - Morizot C | 2011 | Free Radic Biol Med2011，51，8： | 1 |
| 13 | Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans 显示文摘 | COTTART C H VALI-RIE N A BEAUDEUX J L | 2014 | Mol Nutr Food Res2014，58，1： | 1 |
| 14 | TNF-ct/1L- 2 ratio discriminates latent from active tuberculosis in immunocompetent children: a pilot study 显示文摘 | GourgouiUon N de Lauzanne A Cottart CH | 2012 | Pediatr Res2012，72，4： | 1 |
| 15 | Review of recent data on the metabolism,biological effects,and toxicity of resveratrol in humans显示文摘 | Cottart CH Nivet-Antoine V Beaudeux JL | 2014 | Mol Nutr Food Res2014，58，1： | 1 |
| 16 | Resveratrol bioavailability and toxicity in humans显示文摘 | Cottart CH Laguillier-Morizot C Nivet-Antoine V | 2010 | Mol Nutr Res2010，54，1： | 1 |
| 17 | Simple spectrophotometric assessment of the trans-/cis-resvemtrol ratio in aqueous solutions 显示文摘 | CAMONT L COTTART CH RHAYEM Y | 2009 | Anal Chim Acta2009，634，1： | 1 |
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