Analysis of human CD59 tissue expression directed by the CMV-IE-1 promoter in transgenic rats.
The investigation of human complement (C) inhibitors with a view to overcoming C-mediated tissue injury stands to benefit from the production of anatomically suitable transgenic animals. In this study, we used the CMV-IE1 enhancer/promoter to control the expression in vivo in transgenic rats of the human terminal C protein inhibitor CD59. Five transgenic rats were identified, of which four possessed at least one complete copy of the transgene. The presence of human CD59 transcripts and protein was demonstrated in two transgenic rat lines. A widespread tissue distribution of cells expressing human CD59, similar in the two lines, was observed-principally in pancreas, brain, heart, kidney, intestine and striated muscle. Whereas expression in pancreas and brain was uniform, mosaicism of CD59 expression was observed in some tissues such as heart and kidney, a proportion of cells within the tissue not expressing the transgene. Immunohistological analysis revealed surface expression of human CD59 in a variety of cells, including fibroblasts, epithelial cells and muscle cells, but not in endothelial cells. In conclusion, this paper analyses at the cellular level human CD59 expression directed by the CMV promoter in transgenic rats, amd discusses how they could be used to investigate in vivo the role of C in a variety of pathologies.
Charreau
B
B
INSERUM U437, Nantes, France.
Tesson
L
L
Buscail
J
J
Soulillou
J P
JP
Anegon
I
I
D000818:Animals; D030801:Animals, Genetically Modified; D018957:CD59 Antigens / Q000096:biosynthesis* / Q000235:genetics*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D003587:Cytomegalovirus / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D008297:Male; D011401:Promoter Regions, Genetic; D051381:Rats / Q000235:genetics*; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D014018:Tissue Distribution; D014764:Viral Proteins
D018957:CD59 Antigens; D002352:Carrier Proteins; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D011994:Recombinant Proteins; D014764:Viral Proteins; C020723:citrate-binding transport protein