Production and characterization of a pig line transgenic for human membrane cofactor protein.
A pig line transgenic for human membrane cofactor protein (hMCP) has been established. Offspring from the founder were produced by crossing the founder with pigs heterozygous for the human decay accelerating factor (hDAF) transgene. As a result, pigs transgenic for both hMCP and hDAF have been produced. Ribonuclease protection assay (RPA) indicated that hMCP was expressed in all the tissues analysed. In addition, immunohistochemical results indicated a high level of expression of hMCP on neural tissues and islets where hDAF was absent or weakly expressed. C3 fragment deposition and cytotoxicity assays indicated that hMCP expression alone on pig endothelial cells and peripheral blood lymphocytes (PBLs) provided protection against human complement mediated damage. However, we did not find that porcine endothelial cells expressing both hDAF and hMCP were better protected than those expressing hDAF alone. The expression of hMCP on tissues where hDAF is not expressed could provide these tissues with protection against human complement mediated lysis.
Zhou
Chun-Yan
CY
Imutran Ltd (A Novartis Pharma AG Co.), Cambridge, UK. chunyanzhou@bjmu.edu
McInnes
Elizabeth
E
Parsons
Nicola
N
Langford
Gillian
G
Lancaster
Richard
R
Richards
Andrew
A
Pino-Chavez
Gilda
G
Dos Santos Cruz
Gabriela
G
Copeman
Laura
L
Carrington
Christine
C
Thompson
Simon
S
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics* / Q000276:immunology*; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000235:genetics*; D018958:CD55 Antigens / Q000235:genetics; D003176:Complement C3 / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology; D015870:Gene Expression; D005818:Genetic Engineering; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics*; D013552:Swine / Q000235:genetics* / Q000276:immunology*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D003176:Complement C3; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins