Depletion of intercalated cells from collecting ducts of carbonic
anhydrase ii deficient (car2 null) mice .
Breton, Sylvie, Seth L. Alper, Stephen L. Gluck, William S. Sly, Jane
E. Barker, and Dennis Brown.
Renal Unit and Dept. of Pathology, Massachusetts General Hospital
and Harvard Medical School, Boston, MA 02114; Molecular Medicine and
Renal Units, Beth Israel Hospital, Boston, and Dept. of Cell Biology,
Harvard Medical School; Renal Division, Dept. of Internal Medicine,
and George M. O'Brien Center for Developmental Nephrology, Washington
University, School of Medicine, St. Louis. MO; Dept. Biochem., Molec.
Biol., Washington University, St. Louis, MO; The Jackson Laboratory,
Bar Harbor
APStracts 2:0094F, 1995.
The kidneys of mice that are genetically devoid of carbonic anhydrase
type II (CAR2 null mice) were screened by immunocytochemistry with
antibodies that distinguish intercalated and principal cells.
Immunofluorescent localization of the anion exchanger AE1 and of the
56 kD subunit of the vacuolar H+ATPase was used to identify
intercalated cells, while the AQP2 water channel was used as a
specific marker for principal cells of the collecting duct. The CAII
deficiency of the CAR2 null mice was first confirmed by the absence
of immunofluorescent staining of kidney sections exposed to an anti
-CAII antibody. Cells positive for AE1 and H+ATPase were common in all
collecting duct regions in normal mice, but were virtually absent
from the inner stripe of the outer medulla and the inner medulla of
CAR2 null mice. The number of positive cells was also reduced 3-fold
in the cortical collecting duct of CAR2 null animals compared to
normal mice. In parallel, the percentage of AQP2 positive cells was
correspondingly increased in the collecting tubules of CAII-deficient
mice, while the total number of cells per tubule remained unchanged.
These results suggest that intercalated cells are severely depleted
and are replaced by principal cells in CAII-deficient mice.
Quantitative analysis and double staining showed that, in the cortex,
both A and B types of intercalated cells are equally affected.
Elucidation of the mechanism(s) responsible for this phenotype will
be of importance in understanding the origin and development of
intercalated cells in the kidney.
Received 12 December 1994; accepted in final form 23 May 1995.
APS Manuscript Number F439-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.