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The protease renin is the key enzyme in the renin-angiotensin system (RAS) that regulates extracellular volume and blood pressure. Renin is synthesized in renal juxtaglomerular cells (JG cells) as the inactive precursor prorenin. Activation of prorenin by cleavage of the prosegment occurs in renin storage vesicles that have lysosomal properties. To characterize the renin storage vesicles more precisely, the expression and functional relevance of the major lysosomal membrane proteins lysosomal-associated membrane protein 1 (LAMP-1), LAMP-2, and lysosomal integral membrane protein 2 (LIMP-2) were determined in JG cells. Immunostaining experiments revealed strong coexpression of renin with the LIMP-2 (SCARB2), while faint staining of LAMP-1 and LAMP-2 was detected in some JG cells only. Stimulation of the renin system (ACE inhibitor, renal hypoperfusion) resulted in the recruitment of renin-producing cells in the afferent arterioles and parallel upregulation of LIMP-2, but not LAMP-1 or LAMP-2. Despite the coregulation of renin and LIMP-2, LIMP-2-deficient mice had normal renal renin mRNA levels, renal renin and prorenin contents, and plasma renin and prorenin concentrations under control conditions and in response to stimulation with a low salt diet (with or without angiotensin-converting enzyme (ACE) inhibition). No differences in the size or number of renin vesicles were detected using electron microscopy. Acute stimulation of renin release by isoproterenol exerted similar responses in both genotypes in vivo and in isolated perfused kidneys. Renin and the major lysosomal protein LIMP-2 are colocalized and coregulated in renal JG cells, further corroborating the lysosomal nature of renin storage vesicles. LIMP-2 does not appear to play an obvious role in the regulation of renin synthesis or release.

Results of neonatal screening for phenylketonuria (PKU) suggest a west-east gradient of PKU gene frequency in central Europe. In order to test the hypothesis that the unexpectedly high prevalence of PKU in northwestern Germany (northern region of the FRG) is due to the migration of Germans from eastern regions of prewar Germany in the decade after World War II, grandparental origin was determined in a group of 87 pediatric PKU patients and in a control group of 210 children. Grandparents of east German origin were significantly more frequent among the PKU patients. The observed frequency distribution of grandparental subgroups was described by a theoretical distribution in order to obtain a likely set of values for the ratio between the frequency of the PKU gene in the autochthonous populations of prewar northeastern and northwestern Germany. The most likely value for the PKU gene frequency ratio was 1.37, which indicates that the prevalence for PKU in prewar northeastern Germany was almost twice as high as in the autochthonous population of the northwest.