Expression of functional decay-accelerating factor (Cd55) in transgenic mice protects against human complement-mediated attack1

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dc.contributor.authorvan Denderen, B.
dc.contributor.authorPearse, M.
dc.contributor.authorKaterelos, M.
dc.contributor.authorNottle, M.
dc.contributor.authorDu, Z.T.
dc.contributor.authorAminian, A.
dc.contributor.authorAdam, W.
dc.contributor.authorShenoy-Scaria, A.
dc.contributor.authorLublin, D.
dc.contributor.authorShinkel, T.
dc.contributor.authord'Apice, A.
dc.date.issued1996
dc.descriptionCopyright (C) Williams & Wilkins 1996
dc.description.abstractTransgenic mice expressing human CD55 were generated by microinjection of a CD55-minigene under the control of the mouse H2Kb(MHC class I) promoter. Offspring were tested for transgene integration by PCR analysis, and for CD55 expression on peripheral blood leukocytes (PBLs) by flow cytometry. Expression levels of 15 founders ranged from 30 to 80% of that on human neutrophils. Immunohistochemical analysis of kidney, heart, liver, and lung tissue demonstrated staining for CD55 on endothelial surfaces as well as general diffuse staining throughout the tissues. The capacity of the transgenically expressed CD55 to prevent human C3 deposition on the surface of mouse splenocytes was assessed by flow cytometry. Cells from hemizygous mice incubated with 10% fresh human serum as a source of natural antibody and complement bound approximately 65% less C3 than control littermates. No further protection was seen using cells from homozygous littermates, and the protective effect was abrogated by prior incubation with an anti-CD55 monoclonal antibody. Similarly, transgenic mice were afforded significant protection from human serum-mediated lysis, determined using an LDH release assay. Hearts perfused with human plasma showed no increase in survival time in a modified Langendorff perfusion system, however deposition of human C3c was greatly reduced in transgenic hearts.
dc.description.statementofresponsibilityvan Denderen, Bryce J.W., Pearse, Martin J., Katerelos, Marina, Nottle, Mark B., Du, Zhong-Tau, Aminian, Atousa, Adam, William R., Shenoy-Scaria, Amiya, Lublin, Douglas M., Shinkel, Trixie A. and d'Apice, Anthony J.F.
dc.identifier.citationTransplantation, 1996; 61(4):582-588
dc.identifier.doi10.1097/00007890-199602270-00012
dc.identifier.issn0041-1337
dc.identifier.issn1534-6080
dc.identifier.orcidNottle, M. [0000-0001-7625-5542]
dc.identifier.urihttp://hdl.handle.net/2440/8526
dc.language.isoen
dc.publisherWILLIAMS & WILKINS
dc.source.urihttp://journals.lww.com/transplantjournal/Abstract/1996/02270/Expression_of_Functional_Decay_Accelerating_Factor.12.aspx
dc.subjectMyocardium
dc.subjectSpleen
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectMice, Inbred CBA
dc.subjectMice, Transgenic
dc.subjectHumans
dc.subjectMice
dc.subjectImmunoglobulin G
dc.subjectImmunoglobulin M
dc.subjectH-2 Antigens
dc.subjectTransplantation, Heterologous
dc.subjectImmunohistochemistry
dc.subjectMicroinjections
dc.subjectGene Transfer Techniques
dc.subjectPerfusion
dc.subjectComplement Activation
dc.subjectCytotoxicity, Immunologic
dc.subjectBase Sequence
dc.subjectTransgenes
dc.subjectMolecular Sequence Data
dc.subjectMale
dc.subjectComplement C3c
dc.subjectPromoter Regions, Genetic
dc.subjectCD55 Antigens
dc.titleExpression of functional decay-accelerating factor (Cd55) in transgenic mice protects against human complement-mediated attack1
dc.typeJournal article
pubs.publication-statusPublished

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