Transgenic mice expressing heterologous complement receptor type 1 (CR1) molecules on erythrocytes and uses therefor

1. A transgenic mouse whose genome comprises a polynucleotide encoding human complement receptor 1 (CR1) operably linked to a promoter, wherein the human CR1 molecule is expressed on the surface of erythrocytes of the transgenic mouse, and wherein the human CR1 binds immune complexes.

2. The transgenic mouse of claim 1 , wherein the human CR1 molecule is preferentially expressed on the erythrocytes of the transgenic mouse.

3. The transgenic mouse of claim 1 , wherein the promoter is a GATA-1 promoter.

4. The transgenic mouse of claim 1 , wherein the promoter comprises the GATA-1 promoter and upstream regulatory elements thereof that increase CR1 expression on erythroid cells of the transgenic mouse.

5. The transgenic mouse of claim 1 , wherein the transgenic mouse is homozygous for the polynucleotide.

6. The rodent of claim 1 , wherein the transgenic mouse is heterozygous for the polynucleotide.

7. A method for screening for a bispecific compound capable of reducing the concentration of an agent in the serum and/or circulation of a subject, comprising:

administering a test bispecific compounds to the transgenic mouse of claim 4 ;

determining the ability of a bispecific compound to reduce the concentration of the agent in the serum and/or circulation of the transgenic mouse; and

selecting a bispecific compound that reduces the concentration of the agent in the serum and/or circulation of the transgenic mouse to thereby identify a bispecific compound capable of reducing the concentration of an agent in the serum and/or circulation of a subject.

8. A method for evaluating the ability of a bispecific compound to reduce the concentration of an agent in the serum and/or circulation of a subject comprising:

administering the bispecific compound to a transgenic mouse whose genome comprises a polynucleotide encoding human complement receptor 1 (CR1) operably linked to a promoter, wherein the human CR1 is functionally expressed on erythrocytes of the transgenic mouse; and

determining the ability of the bispecific compound to reduce the concentration of the agent in the serum and/or circulation of the transgenic mouse

to thereby evaluate the ability of the bispecific compound to reduce the concentration of the agent in the serum and/or circulation of the transgenic mouse.

9. The method of claim 7 or 8 , further comprising administering the agent to the transgenic mouse.

10. The method of claim 9 , wherein the agent is a pathogen.

11. The method of claim 9 , wherein the agent is a virus.

12. The method of claim 9 , wherein the agent is a toxin.

13. The method of claim 7 or 8 , wherein the agent is a polynucleotide.

14. The method of claim 9 , wherein the agent is a bacterium.

15. The method of claim 9 , wherein the agent is an auto-antibody associated with an auto-immune disease.

16. The method of claim 7 , or 8 , wherein the bispecific compound is a bispecific compound that binds to human CR1.

17. The method of claim 16 , wherein the bispecific compound is a heteropolymer.

18. The method of claim 16 , wherein the bispecific compound is an antigen-based heteropolymer.

19. The method of claim 7 or 8 , wherein the promoter is a GATA-1 promoter.

20. The method of claim 7 or 8 , wherein the promoter comprises the GATA-1 promoter and an upstream control region activating expression on the erythrocytes of the transgenic mouse.

21. A method for making a transgenic mouse expressing human CR1 on the surface of its erythrocytes comprising:

a) introducing a polynucleotide encoding a human CR1 polypeptide into an egg or an embryo of a mouse, the polynucleotide operably linked to a promoter which causes human CR1 to be expressed on mouse erythrocytes; and

b) allowing the egg or embryo comprising the CR1 polynucleotide to develop to term to thereby produce a transgenic mouse transgenic mouse whose genome comprises a polynucleotide encoding a human CR1 polypeptide operably linked to a promoter, wherein the human CR1 polypeptide is expressed on the surface of erythrocytes of the transgenic mouse and binds immune complexes.

22. A method of producing a transgenic mouse, comprising breeding two transgenic mice, genomes of which comprise a polynucleotide encoding a human CR1 polypeptide operably liked to a promoter to thereby produce an offspring transgenic mouse whose genome comprises a polynucleotide encoding a human CR1 polypeptide operably linked to a promoter, wherein the human CR1 polypeptide is expressed on the surface erythrocytes of the transgenic mouse and binds immune complexes.

23. A method for screening for a bispecific compound capable of binding to human CR1 in the serum and/or circulation of a subject, comprising:

administering a test bispecific compounds to the transgenic mouse of claim 4 ;

determining the ability of a bispecific compound to bind human CR1 in the serum and/or circulation of the transgenic mouse; and

selecting a bispecific compound that binds human CR1 in the serum and/or circulation of the transgenic mouse to thereby identify a bispecific compound capable of binding human CR1 in the serum and/or circulation of a subject.

24. A method for evaluating the ability of a bispecific compound to bind human CR1 in the serum and/or circulation of a subject comprising:

administering the bispecific compound to a transgenic mouse whose genome comprises a polynucleotide encoding human complement receptor 1 (CR1) operably linked to a promoter, wherein the human CR1 is expressed on the surface of erythrocytes of the transgenic mouse; and

determining the ability of the bispecific compound to bind human CR1 in the serum and/or circulation of the transgenic mouse;

to thereby evaluate the ability of the bispecific compound to bind human CR1 in the serum and/or circulation of the transgenic mouse.