Expression of a TNF inhibitor in transgenic mice.
We previously reported that a chimeric protein consisting of the human p55 TNF receptor covalently linked to a murine IgG1 Fc heavy chain acts as an efficient TNF inhibitor, as a result of its high binding affinity for native TNF trimers of both murine and human origin. A transgenic mouse line constitutively expressing the inhibitor from a cytomegalovirus promoter was established. All organs examined expressed the transgene. TNF inhibitory activity was easily detected in plasma of transgenic animals but not in plasma of nontransgenic littermates. This founder line was not found to have any obvious phenotype. Specifically, transgenic mice born to wild-type or transgenic females were indistinguishable from nontransgenic littermates with respect to their size at birth, at three months and at six months of age, with respect to the size and morphology of their lymphoid organs and with respect to their hematocrit, white blood cell count, and differential. Although TNF is known to be constitutively expressed by cells of the thymus and trophoblast, the lack of a clear phenotype in association with the constitutive expression of a TNF inhibitor suggests that TNF may be dispensable in early development.
Peppel
K
K
Howard Hughes Medical Institute, Dallas, TX 75235.
Poltorak
A
A
Melhado
I
I
Jirik
F
F
Beutler
B
B
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D012313:RNA / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D012313:RNA