Normal blood pressure and plasma renin activity in mice lacking the renin-binding protein, a cellular renin inhibitor.
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.
Schmitz
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C
Max-Delbrück-Center for Molecular Medicine, Department of Molecular Biology and Biochemistry, Free University, D-13125 Berlin, Germany. cschmitz@mdc-berlin.de
Gotthardt
M
M
Hinderlich
S
S
Leheste
J R
JR
Gross
V
V
Vorum
H
H
Christensen
E I
EI
Luft
F C
FC
Takahashi
S
S
Willnow
T E
TE
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002238:Carbohydrate Epimerases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D017315:Cilazapril / Q000494:pharmacology; D004792:Enzyme Precursors / Q000097:blood; D015870:Gene Expression; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D012016:Reference Values; D012083:Renin / Q000097:blood* / Q000235:genetics
D002352:Carrier Proteins; D004792:Enzyme Precursors; D017315:Cilazapril; D012083:Renin; D002238:Carbohydrate Epimerases; C024519:N-acyl-D-glucosamine 2-epimerase; C498234:Renbp protein, mouse