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J Biol Chem, Vol. 275, Issue 20, 15357-15362, May 19, 2000
From the In renal extracts, some renin is present as
"high molecular weight renin," a heterodimeric complex of renin
with the 46-kDa renin-binding protein (RnBP), also known as
N-acyl-D-glucosamine 2-epimerase. Because RnBP
specifically inhibits renin activity, the protein was proposed to play
an important role in the regulation of the renin-angiotensin system
(RAS). Using gene targeting, we have generated mice lacking RnBP and
tested this hypothesis in vivo. In particular, we analyzed
biosynthesis, secretion, and activity of renin and other components of
the RAS in mice lacking RnBP. Despite extensive investigations, we were
unable to detect any major effects of RnBP deficiency on the plasma and
renal RAS or on blood pressure regulation. Contrary to previous
hypotheses, we conclude that RnBP does not play a significant role in
the regulation of renin activity in plasma or kidney. However, RnBP knockout mice excrete an abnormal pattern of carbohydrates in the
urine, indicating a role of the protein in renal carbohydrate metabolism.
Normal Blood Pressure and Plasma Renin Activity in Mice Lacking
the Renin-binding Protein, a Cellular Renin Inhibitor*
§,,,,
,
Max-Delbrück-Center for Molecular
Medicine, §§ Department of Molecular Biology and
Biochemistry, Free University, and ** Franz-Volhardt-Clinic,
Humboldt University, D-13125 Berlin, Germany, the Departments of
¶ Medical Biochemistry and Cell Biology, University of
Aarhus, 8000 Aarhus C, Denmark, and ¶¶ Akita
Research Institute for Food and Brewing, Akita 010-1623, Japan
*
This work was supported by grants from the Deutsche
Forschungsgemeinschaft, Klinisch-Pharmakologischer Verbund,
Berlin-Brandenburg, and the Danish Medical Research Council.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Heisenberg fellow of the Deutsche Forschungsgemeinschaft.
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