Expression of rabbit C-reactive protein in transgenic mice

Abstract

C-reactive protein (CRP) is a prototypic acute phase reactant in humans and rabbits whose serum concentration can increase up to 1000-fold following an acute inflammatory stimulus. CRP binds to many phosphate ester-containing compounds including phosphorylcholine, nucleotides, chromatin and snRNP. To examine the in vivo function of this protein, we produced transgenic mice capable of significant CRP synthesis. In contrast to most other vertebrates, mice synthesize CRP in only trace amounts. The transgenic animals express rabbit CRP from either the phosphoenolpyruvate carboxykinase promoter (PEPCK-CRP) or the mouse metallothionein 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 100-200 mu g/mL over a period of 2 days. The two MT-CRP lines examined expressed CRP constitutively which could be further elevated 2-4-fold following an inflammatory stimulus. Transgenic CRP bound phosphorylcholine was pentameric, had a circulating half-life of 30-60 min and was capable of activating mouse complement when bound to a ligand. We conclude that these transgenic lines express CRP with many of the properties of authentic rabbit CRP, and that the expression of CRP can be controlled to be dependent or independent of the acute phase response.