Renal proximal tubule function is preserved in Cftr(tm2cam) deltaF508 cystic fibrosis mice

J Physiol. 2001 Apr 15;532(Pt 2):449-57. doi: 10.1111/j.1469-7793.2001.0449f.x.


1. Changes in proximal tubule function have been reported in cystic fibrosis patients. The aim of this study was to investigate proximal tubule function in the Cftr(tm2cam)deltaF508 cystic fibrosis (CF) mouse model. A range of techniques were used including renal clearance studies, in situ microperfusion, RT-PCR and whole-cell patch clamping. 2. Renal Na(+) clearance was similar in wild-type (1.4 +/- 0.3 microl min(-1), number of animals, N = 12) and CF mice (1.6 +/- 0.4 microl min(-1), N = 7) under control conditions. Acute extracellular volume expansion resulted in significant natriuresis in wild-type (7.0 +/- 0.8 microl min(-1), N = 8) and CF mice (9.3 +/- 1.4 microl min(-1), N = 9); no difference between genotypes was observed. 3. In situ microperfusion revealed that fluid absorptive rate (Jv) was similar under control conditions between wild-type (2.2 +/- 0.4 nl mm(-1) min(-1), n = 10) and CF mice (1.9 +/- 0.3 nl mm(-1) min(-1), n = 11). Addition of a forskolin-dibutyryl cAMP (db-cAMP) cocktail to the perfusate caused no significant change in Jv in either wild-type (2.6 +/- 0.7 nl mm(-1) min(-1), n = 10) or Cftr(tm2cam)deltaF508 mice (2.0 +/- 0.5 nl mm(-1) min(-1), n = 10). 4. CFTR expression was confirmed in samples of outer cortex using RT-PCR. However, no evidence for functional CFTR was obtained when outer cortical cells were stimulated with protein kinase A or forskolin-db-cAMP using whole-cell patch clamping. 5. In conclusion, no functional deficit in proximal tubule function was found in Cftr(tm2cam)deltaF508 mice. This may be a consequence of a lack of whole-cell cAMP-dependent Cl(-) conductance in mouse proximal tubule cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / physiopathology*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Kidney Tubules, Proximal / pathology
  • Kidney Tubules, Proximal / physiopathology*
  • Male
  • Mice
  • Mutation / physiology*
  • Patch-Clamp Techniques
  • Perfusion
  • Plasma Substitutes / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium Chloride / pharmacology


  • Plasma Substitutes
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Sodium Chloride