EXPRESSION OF RABBIT C-REACTIVE PROTEIN IN TRANSGENIC MICE

C-reactive protein (CRP) is a prototypic acute phase reactant in human s and rabbits whose serum concentration can increase up to 1000-fold f ollowing an acute inflammatory stimulus. CRP binds to many phosphate e ster-containing compounds including phosphorylcholine, nucleotides, ch romatin and snRNP. To examine the in vivo function of this protein, we produced transgenic mice capable of significant CRP synthesis. In con trast to most other vertebrates, mice synthesize CRP in only trace amo unts. The transgenic animals express rabbit CRP from either the phosph oenolpyruvate carboxykinase promoter (PEPCK-CRP) or the mouse metallot hionein I promoter (MT-CRP). Manipulating the diet in one of the PEPCK -CRP lines led to a rise in serum CRP levels from < 5 mu g/mL to 100-2 00 mu g/mL over a period of 2 days. The two MT-CRP lines examined expr essed CRP constitutively which could be further elevated 2-4-fold foll owing an inflammatory stimulus. Transgenic CRP bound phosphorylcholine was pentameric, had a circulating half-life of 30-60 min and was capa ble of activating mouse complement when bound to a ligand. We conclude that these transgenic lines express CRP with many of the properties o f authentic rabbit CRP, and that the expression of CRP can be controll ed to be dependent or independent of the acute phase response.