Generation and characterization of transgenic mice expressing cobra venom factor.
Cobra venom factor (CVF), the anticomplementary protein in cobra venom, activates the alternative complement pathway, eventually leading to complement consumption. Here, we describe the development of a transgenic mouse model for CVF. We generated a DNA construct containing the full-length cDNA for single-chain pre-pro-CVF. Expression of CVF was controlled by the alpha(1)-antitrypsin promoter to achieve liver-specific expression. Linearized DNA was microinjected into murine ovary cells (strain CD(2)F(1) (BALB/cxDBA/2J)) and the newborn mice were analyzed for stable integration of CVF DNA. After establishing the transgene, mice were propagated in a BALB/c background. The CVF mRNA was detected in the liver and, in some animals, in the kidney. CVF protein was detected in small amounts in the serum. Serum complement hemolytic activity in CVF-transgenic mice was virtually absent. The concentration of plasma C3 was significantly reduced. The CVF-transgenic animals show no unusual phenotype. They provide an animal model to study the effect of long-term complement depletion by continued activation, as well as the role of complement in host immune response and pathogenesis of disease.
Andrä
Jörg
J
Department of Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany. andrae@chemie.uni-hamburg.de
Halter
Roman
R
Kock
Michael A
MA
Niemann
Heiner
H
Vogel
Carl-Wilhelm
CW
Paul
Dieter
D
D000818:Animals; D003176:Complement C3 / Q000032:analysis; D003165:Complement System Proteins / Q000502:physiology; D004546:Elapid Venoms / Q000032:analysis / Q000235:genetics*; D006461:Hemolysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis
D003176:Complement C3; D004546:Elapid Venoms; D012333:RNA, Messenger; C016310:cobra venom factor; D003165:Complement System Proteins