A transgenic mouse model for studying the clearance of blood-borne pathogens via human complement receptor 1 (CR1)
Repik, Alexander ; Pincus, Steve E. ; Ghiran, Ionita ; Nicholson-Weller, Anne ; Asher, Damon R. ; Cerny, Anna M. ; Casey, Leslie S. ; Jones, S. M. ; Jones, Stephen N. ; Mohamed, Nehal ... show 3 more
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Student Authors
Faculty Advisor
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UMass Chan Affiliations
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Keywords
Antibodies, Bispecific
Antigen-Antibody Complex
Bacteriophage phi X 174
*Blood-Borne Pathogens
*Disease Models, Animal
Dose-Response Relationship, Immunologic
Erythrocytes
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Fluorescence
Papio
Receptors, Complement
Immunology and Infectious Disease
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Abstract
Complement receptor 1 (CR1) on the surface of human erythrocytes facilitates intravascular clearance of complement-opsonized pathogens. The need for complement activation can be circumvented by directly coupling the organism to CR1 using a bispecific monoclonal antibody heteropolymer (HP). Lack of a functional homologue to CR1 on mouse erythrocytes has made it difficult to study HP-dependent clearance of pathogens in small animals. We have developed a transgenic mouse that expresses human CR1 on erythrocytes. CR1 antigen is of appropriate size and in a clustered distribution as confirmed by immunoblotting and fluorescence microscopy, respectively. HP that immobilized bacteriophage PhiX174 prototype pathogen to erythrocyte CR1 of the transgenic mice increased the rate of clearance of the virus compared with HP that bound bacteriophage, but not CR1. This transgenic mouse model will allow evaluation of different HPs for their in vivo efficacy and potential as human therapeutics.
Source
Clin Exp Immunol. 2005 May;140(2):230-40. Link to article on publisher's site