S. Kaneta et al., Renal carbonic anhydrase activity in DBA/2FG-pcy/pcy mice with inherited polycystic kidney disease, EXP ANIM, 48(3), 1999, pp. 161-169
DBA/2FG-pcy/pcy (D2-pcy) mice are a hereditary murine model of slowly progr
essive polycystic kidney disease (PKD) and characterized by the persistent
excretion of acidic urine, in association with polyuria, after weaning. In
this study, the activity of carbonic anhydrase (CA) and if histological dis
tribution in the kidney of D2-pcy mice were investigated by immunohistochem
istry. Significantly higher CA activity was detected in the cytosolic, but
not membrane, fraction of kidney homogenates in 5-week-old D2-pcy mice than
in age-matched control DBA/2 (D2) mice, and a more rapid rate of urine aci
dification was noted in 11-week-old mice when acetazolamide, an inhibitor o
f the enzyme, was administered orally. By immunohistochemistry for the majo
r renal CA isoenzyme (CA II), epithelial cells in the distal straight tubul
es and the cortical collecting ducts were stained intensely, whereas those
of the proximal convoluted tubules had only weak and diffuse staining. The
glomeruli, the proximal straight tubules and the ascending thin limb of Hen
le's loop were almost free from staining. In the cells lining cysts and/or
dilated tubules, CA II activity was well preserved, although the staining i
ntensity was considerably reduced in fully-flattened, lining cells of cysts
, but no difference was found between D2-pcy and D2 mice in any segmental l
ocalization of renal CA II activity. From these results it seems that D2-pc
y mice in the early stages of the cystic disease continue to secrete excess
protons through the CA-mediated reaction that is stimulated for regulation
of acid-base balance in the distal portion of the nephron and the collecti
ng duct in kidney. If also suggests that monitoring urine pH may be useful
in predicting the effects of early interventions on the progression of slow
ly developing renal cysts.