Developmental regulation of cftr expression during human
nephrogenesis.
Devuyst, Olivier, Christopher R. Burrow, Eric M. Schwiebert, William
B. Guggino, and Patricia D. Wilson.
Departments of Medicine (Division of Nephrology) and Physiology,
Johns Hopkins University, Medical School, Baltimore, MD 21205
APStracts 3:0077F, 1996.
CFTR mRNA and protein are expressed in proximal and distal tubules of
the human kidney, but CFTR expression pattern during human
nephrogenesis is unknown. We have now studied CFTR expression in
fetal kidneys by immunohistochemistry and Western blot analysis,
using six antibodies against human CFTR. CFTR was expressed in 12
-week human fetal kidneys, mostly in the apical membrane region of the
ureteric bud epithelial cells. By 15 weeks, CFTR was also diffusely
expressed throughout the cytoplasm of proximal tubules and loops of
Henle. No glomerular staining was seen at any stage. From 15 to 24
weeks of gestation this staining pattern remained constant and also
included immunoreactivity of the transitional epithelium. Western
blot for CFTR was performed on membrane extracts of human fetal
kidneys, using T84 cells as a positive control. A 165 kDa protein
corresponding to the predicted size of CFTR was seen at 13 weeks and
throughout development. We also observed a 75 kDa protein which was
distinctly regulated during development. This protein was detected
with several antibodies against the first half of CFTR (including the
R domain) but not with a C-terminus specific antibody, and had the
predicted size of a functional splice variant of CFTR identified in
the human kidney. These results show the complex regulation of CFTR
during nephrogenesis and raise the question of the respective roles
of the full-length and the splice variant CFTR proteins in the human
kidney.
Received 20 November 1995; accepted in final form 12 Arpil 1996.
APS Manuscript Number F394-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96