Title

A transgenic mouse model for studying the clearance of blood-borne pathogens via human complement receptor 1 (CR1)

UMMS Affiliation

Department of Medicine; Program in Molecular Medicine

Publication Date

4-6-2005

Document Type

Article

Subjects

Animals; 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

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: Clin Exp Immunol. 2005 May;140(2):230-40. Link to article on publisher's site

DOI of Published Version

10.1111/j.1365-2249.2005.02764

Related Resources

Link to article in PubMed

Journal/Book/Conference Title

Clinical and experimental immunology

PubMed ID

15807846