PC2 and 7B2 null mice demonstrate that PC2 is essential for normal pro-CCKprocessing

Analysis of CCK content in extracts of whole forebrain from PC2 and 7B2 nul l mouse brain showed a significant decrease relative to wild-type brains. M ore detailed analysis revealed that CCK 8 amide levels in cerebral cortex a nd forebrain regions were more decreased than in hypothalamus. CCK 8 conten t in PC2 null mouse intestines was identical to control. Null mutant brains contained less CCK 8 than wild type and no other forms were seen when anal yzed by gel filtration chromatography. No brain area examined was completel y devoid of CCK, suggesting that other enzymes can partially compensate for the loss of PC2. This is the first demonstration that any endoprotease is important for CCK processing but also suggest the presence of a redundant s ystem to ensure production of active CCK in the brain. (C) 2000 Academic Pr ess.