Decreased transcription of the sodium phosphate (na-/pi)
transporter gene in the hypophosphatemic (hyp) mouse.
Collins, James F., Lawrence A. Scheving, and Fayez K. Ghishan.
Departments of Pediatrics, Molecular Physiology and Biophysics, and
Pathology, Vanderbilt University School of Medicine, Nashville, TN
37232-2576
APStracts 2:0072F, 1995.
Recently it has been hypothesized that the proximal tubular sodium
-phosphate (Na-/Pi) transporter may play a role in murine X-linked
hypophosphatemic vitamin D-resistant rickets. In the present
investigation, Western blot analysis of renal brush-border membrane
proteins, utilizing polyclonal antisera raised against the mouse Na
-/Pi transporter, revealed a predominant band at 87 kDa in normal and
(Hyp) mice. The intensity of this band was reduced in the (Hyp) mouse
by 4.5-fold ([Hyp]/Normal = 0.22 +/- 0.04, n=3, p<0.05).
Additionally, immunohistochemical analysis of kidney cortex in both
mice localized the protein to the apical membrane of the proximal
tubules. Relative transcription rates of the Na-/Pi transporter gene
in the normal and (Hyp) mouse were then investigated. Nuclear run-on
assays showed a 51 +/- 0.02 % decreased rate of transcription of the
Na-/Pi transporter gene in the (Hyp) mice (n=3). Thus, abnormal
transcriptional control of this gene in the (Hyp) mouse likely plays
a role in X-linked hypophosphatemia.
Received 16 February 1995; accepted in final form 26 April 1995.
APS Manuscript Number F57-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.