inbred cftr mice

Summary

Summary: A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.

Top Publications

  1. Kent G, Oliver M, Foskett J, Frndova H, Durie P, Forstner J, et al. Phenotypic abnormalities in long-term surviving cystic fibrosis mice. Pediatr Res. 1996;40:233-41 pubmed
    ..Liquid-fed Cftr-/- mice were infertile, although some males weaned to a solid diet were fertile before they died. Thus, we have succeeded in using dietary means to prolong the lives of Cftr-/- mice...
  2. van Heeckeren A, Schluchter M, Drumm M, Davis P. Role of Cftr genotype in the response to chronic Pseudomonas aeruginosa lung infection in mice. Am J Physiol Lung Cell Mol Physiol. 2004;287:L944-52 pubmed
    ..Therefore, it appears that any functional defect in CFTR produces comparable inflammatory responses to lung infections with P. aeruginosa...
  3. Larbig M, Jansen S, Dorsch M, Bernhard W, Bellmann B, Dorin J, et al. Residual cftr expression varies with age in cftr(tm1Hgu) cystic fibrosis mice: impact on morphology and physiology. Pathobiology. 2002;70:89-97 pubmed
    ..Therefore, the described model is useful for studying the initial CF lung pathophysiology...
  4. Bleich E, Leonhard Marek S, Beyerbach M, Breves G. Characterisation of chloride currents across the proximal colon in CftrTgH(neoim)1Hgu congenic mice. J Comp Physiol B. 2007;177:61-73 pubmed
    ..In contrast, there was no evidence for alternative chloride conductances in BALB/c WT animals, but we cannot exclude that in WT mice a higher chloride secretion via Cftr-channels may have masked an alternative chloride secretion...
  5. Freedman S, Weinstein D, Blanco P, Martinez Clark P, Urman S, Zaman M, et al. Characterization of LPS-induced lung inflammation in cftr-/- mice and the effect of docosahexaenoic acid. J Appl Physiol (1985). 2002;92:2169-76 pubmed
    ..In contrast, neutrophils and eicosanoids were decreased in cftr-/- but not in WT mice treated with DHA, indicating that the effects of DHA on these inflammatory parameters may be related to correction of the membrane lipid defect...
  6. Clarke L, Stien X, Walker N. Intestinal bicarbonate secretion in cystic fibrosis mice. JOP. 2001;2:263-7 pubmed
    ..Studies to identify the proteins involved in non-CFTR mediated HCO(3)(-) secretion are on-going and potentially will provide targets to correct deficient HCO(3)(-) secretion in the CF intestine...
  7. Charizopoulou N, Wilke M, Dorsch M, Bot A, Jorna H, Jansen S, et al. Spontaneous rescue from cystic fibrosis in a mouse model. BMC Genet. 2006;7:18 pubmed
    ..In order to further investigate whether these genetic differences have an impact on the disease phenotype of cystic fibrosis we characterised the phenotype of the two inbred strains...
  8. Garcia M, Yang N, Quinton P. Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion. J Clin Invest. 2009;119:2613-22 pubmed publisher
  9. Durie P, Kent G, Phillips M, Ackerley C. Characteristic multiorgan pathology of cystic fibrosis in a long-living cystic fibrosis transmembrane regulator knockout murine model. Am J Pathol. 2004;164:1481-93 pubmed
    ..We show, for the first time, that long-lived C578L/6J Cftr(-/-) mice develop manifestations of cystic fibrosis-like disease in all pathologically affected organs in the human form of cystic fibrosis...

More Information

Publications95

  1. De Lisle R, Isom K, Ziemer D, Cotton C. Changes in the exocrine pancreas secondary to altered small intestinal function in the CF mouse. Am J Physiol Gastrointest Liver Physiol. 2001;281:G899-906 pubmed
  2. Ip W, Bronsveld I, Kent G, Corey M, Durie P. Exocrine pancreatic alterations in long-lived surviving cystic fibrosis mice. Pediatr Res. 1996;40:242-9 pubmed
    ..These alterations could be due to the primary cystic fibrosis defect, although secondary factors, such as malnutrition induced by decreased dietary intake or abnormal absorptive capacity, may be responsible...
  3. Blanco P, Salem R, Ollero M, Zaman M, Cluette Brown J, Freedman S, et al. Ethanol administration to cystic fibrosis knockout mice results in increased fatty acid ethyl ester production. Alcohol Clin Exp Res. 2005;29:2039-45 pubmed
    ..These data show an association between CFTR dysfunction and qualitative and quantitative changes in FAEE in liver and pancreas upon ethanol exposure. ..
  4. Haston C, Cory S, Lafontaine L, Dorion G, Hallett M. Strain-dependent pulmonary gene expression profiles of a cystic fibrosis mouse model. Physiol Genomics. 2006;25:336-45 pubmed
    ..These results suggest that the variable severity of CF lung disease in this mouse model is controlled by multiple genetic factors, including those of an immune response. ..
  5. Grubb B, Jones J, Boucher R. Mucociliary transport determined by in vivo microdialysis in the airways of normal and CF mice. Am J Physiol Lung Cell Mol Physiol. 2004;286:L588-95 pubmed
    ..In conclusion, we have developed a versatile, simple in vivo method to measure MCT in both upper and lower airways of mice and larger animals. ..
  6. Leipziger J. CFTR - a gatekeeper for duodenal HCO3- secretion. Acta Physiol (Oxf). 2008;193:309 pubmed publisher
  7. Cowley E, Wang C, Gosselin D, Radzioch D, Eidelman D. Mucociliary clearance in cystic fibrosis knockout mice infected with Pseudomonas aeruginosa. Eur Respir J. 1997;10:2312-8 pubmed
    ..Additionally, the observed differences in particle transport suggest that cystic fibrosis transmembrane conductance regulator knockout mice demonstrate different mucociliary responses to infection. ..
  8. Chernova M, Jiang L, Shmukler B, Schweinfest C, Blanco P, Freedman S, et al. Acute regulation of the SLC26A3 congenital chloride diarrhoea anion exchanger (DRA) expressed in Xenopus oocytes. J Physiol. 2003;549:3-19 pubmed
    ..Thus, pharmacological modulation of DRA might be a useful adjunct treatment of cystic fibrosis. ..
  9. Frizzell R, Pilewski J. Finally, mice with CF lung disease. Nat Med. 2004;10:452-4 pubmed
  10. Fischer H, Schwarzer C, Illek B. Vitamin C controls the cystic fibrosis transmembrane conductance regulator chloride channel. Proc Natl Acad Sci U S A. 2004;101:3691-6 pubmed
    ..The pool of vitamin C in the respiratory tract represents a potential nutraceutical and pharmaceutical target for the complementary treatment of sticky airway secretions by enhancing epithelial fluid secretion. ..
  11. Belfodil R, Barriere H, Rubera I, Tauc M, Poujeol C, Bidet M, et al. CFTR-dependent and -independent swelling-activated K+ currents in primary cultures of mouse nephron. Am J Physiol Renal Physiol. 2003;284:F812-28 pubmed
    ..In KO mice, impairment of the regulatory volume decrease process in DCT and CCT could be due to the loss of an autocrine mechanism, implicating ATP and adenosine, which controls swelling-activated Cl(-) and K(+) channels. ..
  12. Velsor L, Kariya C, Kachadourian R, Day B. Mitochondrial oxidative stress in the lungs of cystic fibrosis transmembrane conductance regulator protein mutant mice. Am J Respir Cell Mol Biol. 2006;35:579-86 pubmed
    ..Further studies are needed to determine how CFTR deficiency contributes to mitochondrial oxidative stress and the role this plays in CFTR-mediated lung pathophysiology. ..
  13. Oceandy D, McMorran B, Schreiber R, Wainwright B, Kunzelmann K. GFP-tagged CFTR transgene is functional in the G551D cystic fibrosis mouse colon. J Membr Biol. 2003;192:159-67 pubmed
    ..Thus, K18-GFP-CFTR is functionally expressed in transgenic mice, which will be a valuable tool in studies on CFTR synthesis, processing and ion transport in native epithelial tissues. ..
  14. De Lisle R. Increased expression of sulfated gp300 and acinar tissue pathology in pancreas of CFTR(-/-) mice. Am J Physiol. 1995;268:G717-23 pubmed
    ..It is suggested that increased expression of gp300 in CFTR(-/-) mice may cause poorly soluble exocrine protein secretion, contributing to the development of CF in the pancreas...
  15. Haston C, Li W, Li A, Lafleur M, Henderson J. Persistent osteopenia in adult cystic fibrosis transmembrane conductance regulator-deficient mice. Am J Respir Crit Care Med. 2008;177:309-15 pubmed
  16. Gyomorey K, Garami E, Galley K, Rommens J, Bear C. Non-CFTR chloride channels likely contribute to secretion in the murine small intestine. Pflugers Arch. 2001;443 Suppl 1:S103-6 pubmed
    ..On the other hand, a basal chloride secretion across the intestinal epithelium was present in these animals, and we hypothesize that this activity may be linked to improved survival of these animals. ..
  17. Guilbault C, Wojewodka G, Saeed Z, Hajduch M, Matouk E, De Sanctis J, et al. Cystic fibrosis fatty acid imbalance is linked to ceramide deficiency and corrected by fenretinide. Am J Respir Cell Mol Biol. 2009;41:100-6 pubmed publisher
    ..We found that fenretinide treatment normalizes the fatty acid imbalance in CF mice with reducing AA to WT levels and increasing DHA. We propose that fenretinide treatment might improve this pathological phenotype in patients with CF. ..
  18. Norkina O, Graf R, Appenzeller P, De Lisle R. Caerulein-induced acute pancreatitis in mice that constitutively overexpress Reg/PAP genes. BMC Gastroenterol. 2006;6:16 pubmed
    ..While Reg/PAP may be protective they may also have a negative effect during pancreatitis due to their anti-apoptotic activity, which has been shown to increase the severity of pancreatitis. ..
  19. Cartiera M, Ferreira E, Caputo C, Egan M, Caplan M, Saltzman W. Partial correction of cystic fibrosis defects with PLGA nanoparticles encapsulating curcumin. Mol Pharm. 2010;7:86-93 pubmed publisher
    ..Our results suggest that oral administration of PLGA nanoparticles encapsulating curcumin enhances the effects of curcumin therapy in CF mice, as compared to delivery of nonencapsulated curcumin. ..
  20. Davidson D, Webb S, Teague P, Govan J, Dorin J. Lung pathology in response to repeated exposure to Staphylococcus aureus in congenic residual function cystic fibrosis mice does not increase in response to decreased CFTR levels or increased bacterial load. Pathobiology. 2004;71:152-8 pubmed
    ..aureus, suggesting a critical threshold level for functional CFTR. ..
  21. Lu M, Dong K, Egan M, Giebisch G, Boulpaep E, Hebert S. Mouse cystic fibrosis transmembrane conductance regulator forms cAMP-PKA-regulated apical chloride channels in cortical collecting duct. Proc Natl Acad Sci U S A. 2010;107:6082-7 pubmed publisher
    ..We discuss the physiologic implications of open CFTR Cl(-) channels on salt handling by the collecting duct and on the functional CFTR-ROMK interactions in modulating the metabolic ATP-sensing of ROMK. ..
  22. Zsembery A, Hargitai D. Role of Ca2+ -activated ion transport in the treatment of cystic fibrosis. Wien Med Wochenschr. 2008;158:562-4 pubmed publisher
    ..Importantly, the increase in [Ca(2+)](i) stimulates anion secretion of nasal epithelia in CF mouse models suggesting that targeting P2X receptors might have beneficial effects in CF therapy. ..
  23. Scheid P, Kempster L, Griesenbach U, Davies J, Dewar A, Weber P, et al. Inflammation in cystic fibrosis airways: relationship to increased bacterial adherence. Eur Respir J. 2001;17:27-35 pubmed
    ..The authors conclude that the stimulus produced by Pseudomonas aeruginosa is the predominant inflammatory trigger in their models. ..
  24. De Lisle R, Petitt M, Huff J, Isom K, Agbas A. MUCLIN expression in the cystic fibrosis transmembrane conductance regulator knockout mouse. Gastroenterology. 1997;113:521-32 pubmed
  25. Clarke L, Gawenis L, Bradford E, Judd L, Boyle K, Simpson J, et al. Abnormal Paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice. Am J Physiol Gastrointest Liver Physiol. 2004;286:G1050-8 pubmed
    ..Based on these findings, we conclude that antimicrobial peptide activity in CF mouse intestine is compromised by inadequate dissolution of Paneth cell granules within the crypt lumens. ..
  26. Cottart C, Bonvin E, Rey C, Wendum D, Bernaudin J, Dumont S, et al. Impact of nutrition on phenotype in CFTR-deficient mice. Pediatr Res. 2007;62:528-32 pubmed
    ..These effects of diet are important to consider in future animal studies and also prompt to evaluate high-energy diets in CF patients. ..
  27. Cohen J, Lundblad L, Bates J, Levitzky M, Larson J. The "Goldilocks effect" in cystic fibrosis: identification of a lung phenotype in the cftr knockout and heterozygous mouse. BMC Genet. 2004;5:21 pubmed
    ..Distinct phenotypes were demonstrated in each genotype, cftr-/-, cftr +/-, and cftr+/+. These results are consistent with a developmental role for CFTR in the lung. ..
  28. Fortner C, Lorenz J, Paul R. Chloride channel function is linked to epithelium-dependent airway relaxation. Am J Physiol Lung Cell Mol Physiol. 2001;280:L334-41 pubmed
    ..This work introduces a possible role for Cl- pathways in the modulation of airway smooth muscle function and may have implications for fundamental studies of airway function as well as therapeutic approaches to pulmonary disease...
  29. Dif F, Djediat C, Alegria O, Demeneix B, Levi G. Transfection of multiple pulmonary cell types following intravenous injection of PEI-DNA in normal and CFTR mutant mice. J Gene Med. 2006;8:82-9 pubmed
    ..The results demonstrate that PEI-mediated gene delivery leads to transfection of epithelial cells beyond the endothelial barrier and show that this method can be used for lung gene delivery in CF fragile mutant mice. ..
  30. Gallagher A, Gottlieb R. Proliferation, not apoptosis, alters epithelial cell migration in small intestine of CFTR null mice. Am J Physiol Gastrointest Liver Physiol. 2001;281:G681-7 pubmed
    ..Thus increased proliferation but not alterations in apoptosis within epithelial cells might contribute to the pathophysiology of CF...
  31. Bruscia E, Zhang P, Barone C, Scholte B, Homer R, Krause D, et al. Increased susceptibility of Cftr-/- mice to LPS-induced lung remodeling. Am J Physiol Lung Cell Mol Physiol. 2016;310:L711-9 pubmed publisher
    ..This study shows that chronic inflammation alone contributes significantly to aspects of CF lung pathology. ..
  32. Barriere H, Tauc M, Poujeol P. Use of knock-out mouse models for the study of renal ion channels. J Membr Biol. 2004;198:113-24 pubmed
  33. Xie C, Cao X, Chen X, Wang D, Zhang W, Sun Y, et al. Mechanosensitivity of wild-type and G551D cystic fibrosis transmembrane conductance regulator (CFTR) controls regulatory volume decrease in simple epithelia. FASEB J. 2016;30:1579-89 pubmed publisher
    ..Zhang, W. K., Sun, Y., Hu, W., Zhou, Z., Wang, Y., Huang, P. Mechanosensitivity of wild-type and G551D cystic fibrosis transmembrane conductance regulator (CFTR) controls regulatory volume decrease in simple epithelia. ..
  34. L Hoste S, Chargui A, Belfodil R, Duranton C, Rubera I, Mograbi B, et al. CFTR mediates cadmium-induced apoptosis through modulation of ROS level in mouse proximal tubule cells. Free Radic Biol Med. 2009;46:1017-31 pubmed publisher
    ..Our data suggest that CFTR could modulate ROS levels to ensure apoptosis during Cd(2+) exposure by modulating the intracellular content of glutathione. ..
  35. Norkina O, Kaur S, Ziemer D, De Lisle R. Inflammation of the cystic fibrosis mouse small intestine. Am J Physiol Gastrointest Liver Physiol. 2004;286:G1032-41 pubmed
    ..Immune cell infiltration was confirmed histologically by staining for mast cells and neutrophils. These data demonstrate that the CF intestine exhibits an inflammatory state with upregulation of components of the innate immune system. ..
  36. Lu M, Leng Q, Egan M, Caplan M, Boulpaep E, Giebisch G, et al. CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney. J Clin Invest. 2006;116:797-807 pubmed
    ..We discuss the potential physiological role of this functional switch in renal K handling during water diuresis and the relevance to renal K homeostasis in cystic fibrosis...
  37. Malmberg E, Noaksson K, Phillipson M, Johansson M, Hinojosa Kurtzberg M, Holm L, et al. Increased levels of mucins in the cystic fibrosis mouse small intestine, and modulator effects of the Muc1 mucin expression. Am J Physiol Gastrointest Liver Physiol. 2006;291:G203-10 pubmed
    ..The results suggest that MUC1 is not a major component in the accumulated mucus of CF mice and that MUC1 can influence the amount of other mucins in a still unknown way...
  38. Jones J, Schwiebert E, DuVall M, Venglarik C, Wen H, Kovacs T, et al. Activation of chloride secretion in cystic fibrosis cells and tissues by the substituted imidazole SRI 2931. Biochemistry. 2003;42:13241-9 pubmed
    ..The magnitude, longevity, and mechanism of action of the response provide a tool for dissecting pathways of epithelial ATP extracellular signaling and Cl(-) permeability...
  39. Geiser M, Bastian S. Surface-lining layer of airways in cystic fibrosis mice. Am J Physiol Lung Cell Mol Physiol. 2003;285:L1277-85 pubmed
    ..Hence, there were no signs of any ultrastructural abnormalities in the surface-lining layer of young adult Cftrtm1HGU/Cftrtm1HGU mice before infection with CF-related pathogens...
  40. Barker P, Gillie D, Schechter M, Rubin B. Effect of macrolides on in vivo ion transport across cystic fibrosis nasal epithelium. Am J Respir Crit Care Med. 2005;171:868-71 pubmed
    ..We conclude that the apparent beneficial effects of macrolides on pulmonary outcome in CF are not mediated by their modulation of ion transport...
  41. Levin M, Verkman A. CFTR-regulated chloride transport at the ocular surface in living mice measured by potential differences. Invest Ophthalmol Vis Sci. 2005;46:1428-34 pubmed
    ..To define the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in Cl(-) secretion at the mouse ocular surface in vivo...
  42. Guilbault C, Martin P, Houle D, Boghdady M, Guiot M, Marion D, et al. Cystic fibrosis lung disease following infection with Pseudomonas aeruginosa in Cftr knockout mice using novel non-invasive direct pulmonary infection technique. Lab Anim. 2005;39:336-52 pubmed
    ..aeruginosa. Overall, this method simplifies the infection procedure in terms of its duration and invasiveness, and improves the survival rate of the KO mice when compared with the previously used intratracheal procedure...
  43. Robert R, Norez C, Becq F. Disruption of CFTR chloride channel alters mechanical properties and cAMP-dependent Cl- transport of mouse aortic smooth muscle cells. J Physiol. 2005;568:483-95 pubmed
    ..To our knowledge this study is the first to report the phenotypic consequences of the loss of a Cl(-) channel on vascular reactivity...
  44. Thomopoulos G, Shori D, Asking B, Kosta A, Dimopoulou A, Paterson K, et al. Ultrastructural changes in exocrine tissues of a DeltaF-508 CFTR mouse model. Pflugers Arch. 2001;443 Suppl 1:S28-35 pubmed
  45. Seidler U, Singh A, Chen M, Cinar A, Bachmann O, Zheng W, et al. Knockout mouse models for intestinal electrolyte transporters and regulatory PDZ adaptors: new insights into cystic fibrosis, secretory diarrhoea and fructose-induced hypertension. Exp Physiol. 2009;94:175-9 pubmed publisher
  46. Li L, He D, Wilborn T, Falany J, Falany C. Increased SULT1E1 activity in HepG2 hepatocytes decreases growth hormone stimulation of STAT5b phosphorylation. Steroids. 2009;74:20-9 pubmed publisher
    ..The enhanced SULT1E1 activity may have a role in inhibiting GH-stimulated STAT5b phosphorylation and IGF-1 synthesis via the sulfation and inactivation of E2...
  47. Li L, Falany C. Elevated hepatic SULT1E1 activity in mouse models of cystic fibrosis alters the regulation of estrogen responsive proteins. J Cyst Fibros. 2007;6:23-30 pubmed
    ..However, the underlying mechanisms of liver disease in CF are poorly understood...
  48. Canale Zambrano J, Poffenberger M, Cory S, Humes D, Haston C. Intestinal phenotype of variable-weight cystic fibrosis knockout mice. Am J Physiol Gastrointest Liver Physiol. 2007;293:G222-9 pubmed
    ..In this CF mouse model, crypt elongation, due to an expanded proliferative zone and decreased apoptosis, was identified to be dependent on body weight...
  49. Wu Y, Abolhassani M, Ollero M, Dif F, Uozumi N, Lagranderie M, et al. Cytosolic phospholipase A2alpha mediates Pseudomonas aeruginosa LPS-induced airway constriction of CFTR -/- mice. Respir Res. 2010;11:49 pubmed publisher
    ..Lungs of cystic fibrosis (CF) patients are chronically infected with Pseudomonas aeruginosa. Increased airway constriction has been reported in CF patients but underplaying mechanisms have not been elucidated...
  50. Pier G. Dropping acid to help cystic fibrosis. Nat Med. 2008;14:367-9 pubmed publisher
  51. Mhanna M, Ferkol T, Martin R, Dreshaj I, van Heeckeren A, Kelley T, et al. Nitric oxide deficiency contributes to impairment of airway relaxation in cystic fibrosis mice. Am J Respir Cell Mol Biol. 2001;24:621-6 pubmed
    ..We conclude that the relative absence of NO compromises airways relaxation in CF, and may contribute to the bronchial obstruction seen in the disease...
  52. Sui W, Boyd C, Wright J. Altered pH regulation during enamel development in the cystic fibrosis mouse incisor. J Dent Res. 2003;82:388-92 pubmed
    ..These results indicate that CFTR plays a role in pH regulation during enamel development and that a reduced pH results in a lack of calcium influx during enamel maturation and hypomineralization of the CF incisor enamel...
  53. Gonzalez Zorn B, Senna J, Fiette L, Shorte S, Testard A, Chignard M, et al. Bacterial and host factors implicated in nasal carriage of methicillin-resistant Staphylococcus aureus in mice. Infect Immun. 2005;73:1847-51 pubmed
    ..aureus strains and demonstrated increased colonization levels by MRSA in cystic fibrosis transmembrane conductance regulator-deficient mice and Toll-like receptor 2 (TLR2)-deficient mice but not TLR4-deficient mice...
  54. Wallace H, Connell M, Losty P, Jesudason E, Southern K. Embryonic lung growth is normal in a cftr-knockout mouse model. Exp Lung Res. 2008;34:717-27 pubmed publisher
    ..Smooth muscle distribution surrounding the airway appeared normally distributed in all genotypes. These data suggest that normal embryonic lung growth, ASM differentiation and airway peristalsis are CFTR independent...
  55. Toth B, Leonhard Marek S, Hedrich H, Breves G. Characterisation of electrogenic nutrient absorption in the Cftr TgH(neoim)Hgu mouse model. J Comp Physiol B. 2008;178:705-12 pubmed publisher
    ..The electrogenic absorption of alanine, glycyl-glutamine and glucose was not influenced by an acidic pH (5.4) compared to absorption at pH 7.4...
  56. Kozlova I, Nilsson H, Phillipson M, Riederer B, Seidler U, Colledge W, et al. X-ray microanalysis of airway surface liquid in the mouse. Am J Physiol Lung Cell Mol Physiol. 2005;288:L874-8 pubmed
    ..It is concluded that mouse ASL under unstimulated conditions is hypotonic, which may be related to the relative paucity of submucosal glands in the mouse trachea...
  57. Beharry S, Ackerley C, Corey M, Kent G, Heng Y, Christensen H, et al. Long-term docosahexaenoic acid therapy in a congenic murine model of cystic fibrosis. Am J Physiol Gastrointest Liver Physiol. 2007;292:G839-48 pubmed
    ..The potential therapeutic benefits of DHA in severe CF-associated liver disease remain to be explored...
  58. Best J, Quinton P. Salivary secretion assay for drug efficacy for cystic fibrosis in mice. Exp Physiol. 2005;90:189-93 pubmed
    ..The data indicate that salivary secretory rates in CF mice could be used to assay potential drugs for their effectiveness in correcting the secretory defect in cystic fibrosis...
  59. Kibble J, Neal A, Colledge W, Green R, Taylor C. Evidence for cystic fibrosis transmembrane conductance regulator-dependent sodium reabsorption in kidney, using Cftr(tm2cam) mice. J Physiol. 2000;526 Pt 1:27-34 pubmed
    ..Enhanced amiloride-sensitive FE(Na) is consistent with increased Na(+) absorption via the amiloride-sensitive sodium channel ENaC, in cystic fibrosis kidney, but this was only observed during salt restriction...
  60. Hinojosa Kurtzberg A, Johansson M, Madsen C, Hansson G, Gendler S. Novel MUC1 splice variants contribute to mucin overexpression in CFTR-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2003;284:G853-62 pubmed
    ..Thus MUC1 expression is increased, and it appears that alternate cytoplasmic tails may change its role in signaling. MUC1 could be an important contributor to the CF intestinal phenotype...
  61. Ghosal S, Taylor C, Colledge W, Ratcliff R, Evans M. Sodium channel blockers and uridine triphosphate: effects on nasal potential difference in cystic fibrosis mice. Eur Respir J. 2000;15:146-50 pubmed
    ..More stable analogues of uridine triphosphate in combination with long acting sodium channel blockers such as loperamide may have therapeutic potential in cystic fibrosis...
  62. Day B, van Heeckeren A, Min E, Velsor L. Role for cystic fibrosis transmembrane conductance regulator protein in a glutathione response to bronchopulmonary pseudomonas infection. Infect Immun. 2004;72:2045-51 pubmed
    ..Individuals with lung diseases associated with altered antioxidant transport, such as cystic fibrosis, might lack the ability to adapt to the infection and present with a more severe inflammatory response...
  63. Deriy L, Gomez E, Zhang G, Beacham D, Hopson J, Gallan A, et al. Disease-causing mutations in the cystic fibrosis transmembrane conductance regulator determine the functional responses of alveolar macrophages. J Biol Chem. 2009;284:35926-38 pubmed publisher
  64. Weiner S, Caputo C, Bruscia E, Ferreira E, Price J, Krause D, et al. Rectal potential difference and the functional expression of CFTR in the gastrointestinal epithelia in cystic fibrosis mouse models. Pediatr Res. 2008;63:73-8 pubmed
    ..The data suggest that the in vivo RPD assay is a reliable assay of functional CFTR expression in CF mouse models...
  65. Kuver R, Wong T, Klinkspoor J, Lee S. Absence of CFTR is associated with pleiotropic effects on mucins in mouse gallbladder epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2006;291:G1148-54 pubmed
    ..Secreted mucins from Cftr((-/-)) cells contained higher sulfate concentrations. Thus absence of CFTR is associated with pleiotropic effects on mucins in murine GBEC...
  66. Ianowski J, Choi J, Wine J, Hanrahan J. Substance P stimulates CFTR-dependent fluid secretion by mouse tracheal submucosal glands. Pflugers Arch. 2008;457:529-37 pubmed publisher
    ..Since CFTR regulation is qualitatively similar in human and mouse glands, loss of this local regulation in CF may contribute to reduced innate defenses in CF airways...
  67. Liang L, MacDonald K, Schwiebert E, Zeitlin P, Guggino W. Spiperone, identified through compound screening, activates calcium-dependent chloride secretion in the airway. Am J Physiol Cell Physiol. 2009;296:C131-41 pubmed publisher
    ..In conclusion, we have identified spiperone as a new therapeutic platform for correction of defective Cl(-) secretion in CF via a pathway independent of CFTR...
  68. Falany C, He D, Li L, Falany J, Wilborn T, Kocarek T, et al. Regulation of hepatic sulfotransferase (SULT) 1E1 expression and effects on estrogenic activity in cystic fibrosis (CF). J Steroid Biochem Mol Biol. 2009;114:113-9 pubmed publisher
    ..The changes in hepatocyte gene expression affect liver biochemistry and may facilitate the development of CF liver disease...
  69. Jayaraman S, Song Y, Verkman A. Airway surface liquid osmolality measured using fluorophore-encapsulated liposomes. J Gen Physiol. 2001;117:423-30 pubmed
    ..ASL fluid is approximately isosmolar under normal physiological conditions, but can become hyperosmolar when exposed to dry air, which may induce cough and airway reactivity in some patients...
  70. Carvalho Oliveira I, Charro N, Aarbiou J, Buijs Offerman R, Wilke M, Schettgen T, et al. Proteomic analysis of naphthalene-induced airway epithelial injury and repair in a cystic fibrosis mouse model. J Proteome Res. 2009;8:3606-16 pubmed publisher
    ..Further, the results suggest the involvement of prostaglandin and retinoic acid metabolism in the abnormal responses of CF mutant mice to injury...
  71. Freudenberg F, Leonard M, Liu S, Glickman J, Carey M. Pathophysiological preconditions promoting mixed "black" pigment plus cholesterol gallstones in a DeltaF508 mouse model of cystic fibrosis. Am J Physiol Gastrointest Liver Physiol. 2010;299:G205-14 pubmed publisher
    ..This is an initial step toward unraveling the molecular basis of CF gallstone disease and constitutes a framework for investigating animal models of CF with more severe biliary disease, as well as the human disease...
  72. Davis P, Drumm M. Some like it hot: curcumin and CFTR. Trends Mol Med. 2004;10:473-5 pubmed
    ..Although other laboratories have not been able to confirm the initial observations, activating DeltaF508 CFTR could have such important therapeutic implications that a thorough investigation of the potential of curcumin is warranted...
  73. Ishiguro H, Steward M, Naruse S, Ko S, Goto H, Case R, et al. CFTR functions as a bicarbonate channel in pancreatic duct cells. J Gen Physiol. 2009;133:315-26 pubmed publisher
    ..This suggests that CFTR functions as a HCO(3)(-) channel in pancreatic duct cells, and that it provides a significant pathway for HCO(3)(-) transport across the apical membrane...
  74. Stelzner M, Somasundaram S, Lee S, Kuver R. Ileal mucosal bile acid absorption is increased in Cftr knockout mice. BMC Gastroenterol. 2001;1:10 pubmed
  75. Hodges C, Cotton C, Palmert M, Drumm M. Generation of a conditional null allele for Cftr in mice. Genesis. 2008;46:546-52 pubmed publisher
    ..Mice containing the conditional null Cftr allele will be useful in future studies to understand the role of Cftr in specific tissues and developmental time points and lead to a better understanding of CF disease...
  76. Bradbury J. Detergent-lentiviral combination gives gene therapy hope for cystic fibrosis. Lancet. 2002;360:1306 pubmed
  77. Knorre A, Wagner M, Schaefer H, Colledge W, Pahl H. DeltaF508-CFTR causes constitutive NF-kappaB activation through an ER-overload response in cystic fibrosis lungs. Biol Chem. 2002;383:271-82 pubmed
    ..This endogenous NF-kappaB activation stimulates the transcription of pro-inflammatory cytokines thereby commencing an inflammatory cascade within the CF lung...
  78. Grubb B, Chadburn J, Boucher R. In vivo microdialysis for determination of nasal liquid ion composition. Am J Physiol Cell Physiol. 2002;282:C1423-31 pubmed
    ..7 +/- 0.4 mM) was significantly less in normal than in CF mice (16.6 +/- 4 mM). IVMD accurately samples nasal liquid for ionic composition. The ionic composition of nasal liquid in the normal and CF mice is similar...
  79. Arquitt C, Boyd C, Wright J. Cystic fibrosis transmembrane regulator gene (CFTR) is associated with abnormal enamel formation. J Dent Res. 2002;81:492-6 pubmed
    ..05) in the CF mature enamel. Abnormal enamel mineralization, ion concentrations, and molecular evidence of cftr mRNA expression by odontogenic cells strongly suggest that CFTR plays an important role in enamel formation...
  80. Ollero M, Laposata M, Zaman M, Blanco P, Andersson C, Zeind J, et al. Evidence of increased flux to n-6 docosapentaenoic acid in phospholipids of pancreas from cftr-/- knockout mice. Metabolism. 2006;55:1192-200 pubmed
    ..This suggests an enhanced flux through the n-6 pathway beyond arachidonate. This study provides a more in-depth understanding of the fatty acid alterations found in CF, as reflected by the cftr(-/-) mouse model...
  81. Paradis J, Wilke M, Haston C. Osteopenia in Cftr-deltaF508 mice. J Cyst Fibros. 2010;9:239-45 pubmed publisher
    ..To determine whether this phenotype is present in cystic fibrosis mouse models with the DeltaF508 Cftr mutation we assessed the femora of adult FVB/N Cftr(tm1Eur) and C57BL/6 Cftr(tm1Kth) mice...
  82. Luciani A, Villella V, Esposito S, Brunetti Pierri N, Medina D, Settembre C, et al. Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition. Nat Cell Biol. 2010;12:863-75 pubmed publisher
    ..Restoring beclin 1 or knocking down p62 rescued the trafficking of CFTR(F508del) to the cell surface. These data link the CFTR defect to autophagy deficiency, leading to the accumulation of protein aggregates and to lung inflammation...
  83. Croft N. The spice of life for cystic fibrosis. Gastroenterology. 2004;127:1639-40 pubmed
  84. De Lisle R, Sewell R, Meldi L. Enteric circular muscle dysfunction in the cystic fibrosis mouse small intestine. Neurogastroenterol Motil. 2010;22:341-e87 pubmed publisher
    ..CONCLUSIONS & INFERENCES These results suggest that the enteric microbiota modulates PGE(2) levels in a complex manner, which affects enteric smooth muscle activity and contributes to slower small intestinal transit in CF...
  85. Guilbault C, Novak J, Martin P, Boghdady M, Saeed Z, Guiot M, et al. Distinct pattern of lung gene expression in the Cftr-KO mice developing spontaneous lung disease compared with their littermate controls. Physiol Genomics. 2006;25:179-93 pubmed
    ..These findings point to distinct mechanisms of gene expression regulation between mice with CF and control mice...
  86. Levin M, Kim J, Hu J, Verkman A. Potential difference measurements of ocular surface Na+ absorption analyzed using an electrokinetic model. Invest Ophthalmol Vis Sci. 2006;47:306-16 pubmed