In renal extracts, some renin is present as "high molecular weight renin,"
a heterodimeric complex of renin with the 46-kDa renin-binding protein (RnB
P), also known as N-acyl-D-glucosamine a-epimerase. Because RnBP specifical
ly inhibits renin activity, the protein was proposed to play an important r
ole in the regulation of the renin-angiotensin system (RAS), Using gene tar
geting, we have generated mice lacking RnBP and tested this hypothesis in v
ivo. In particular, we analyzed biosynthesis, secretion, and activity of re
nin and other components of the RAS in mice lacking RnBP, Despite extensive
investigations, we were unable to detect any major effects of RnBP deficie
ncy on the plasma and renal RAS or on blood pressure regulation. Contrary t
o previous hypotheses, we conclude that RnBP does not play a significant ro
le in the regulation of renin activity in plasma or kidney, However, RnBP k
nockout mice excrete an abnormal pattern of carbohydrates in the urine, ind
icating a role of the protein in renal carbohydrate metabolism.