Renal proximal tubule function is preserved in Cftrtm2cam ΔF508 cystic fibrosis mice

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) Delta F508 cystic fibrosis (CP) mouse model. B range of techniques were used including renal clearance studies, in situ microperfusion, RT-PCR and whole-cell patch clamping. 2. Penal Na+ clearance was similar in wild-type (1.4 +/- 0.3 mul 1 min(-1), number of animals, N = 12) and CP mice (1.6 +/- 0.4 mul min(-1), N = 7) under control conditions. Acute extracellular volume expansion resulted in significant natriuresis in wild-type (7.0 +/- 0.8 mul min(-1), N = 8) and CF mice (9.3 +/- 1.4 mul min(-1), N= 9); no difference between genotypes was observed. 3. In Situ microperfusion revealed that fluid absorptive rate (J(v)) was similar under control conditions between wild-type (2.2 +/- 0.4 nl mm(-1) min(-1), n = 10) and CP 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 J(v) in either wild-type (2.6 +/- 0.7 nl mm(-1) min(-1), n = 10) or Cftr(tm2cam) Delta B508 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(tm25cam) Delta F508 mice. This may be a consequence of a lack of whole-cell cAMP-dependent Cl- conductance in mouse proximal tubule cells.