Humanized c5 animals

Abstract

Non-human animals comprising a human or humanized C3 and/or C5 nucleic acid sequence are provided as well as methods for using the same to identify compounds capable of modulating the complement system. Non-human animals that comprise a replacement of the endogenous C5 gene and/or C3 gene with a human or humanized C5 gene and/or C3 gene, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized C5 gene under control of non-human C5 regulatory elements is also provided, including non-human animals that have a replacement of non-human C5-encoding sequence with human C5-encoding sequence at an endogenous non-human C5 locus. Non-human animals comprising a human or humanized C3 gene under control of non-human C3 regulatory elements is also provided, including non-human animals that have a replacement of non-human C3 protein-encoding sequence with human or humanized C3 protein-encoding sequence at an endogenous non-human C3 locus. Non-human animals comprising human or humanized C3 and/or C5 sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

1 .- 20 . (canceled) 
     
     
         21 . An isolated rodent cell, whose genome comprises
 (i) a replacement of a rodent C3 gene sequence at an endogenous rodent C3 locus with a human C3 gene sequence to form a modified C3 gene, wherein the rodent C3 gene sequence comprises an exon of the endogenous rodent C3 gene and the human C3 gene sequence comprises exon 2 through exon 41 of the human C3 gene;   (ii) a replacement of a rodent C5 gene sequence at an endogenous rodent C5 locus with a human C5 gene sequence to form a modified C5 gene, wherein the rodent C5 gene sequence comprises an exon of the endogenous rodent C5 gene and the human C5 gene sequence comprises exon 2 through exon 41 of the human C5 gene, wherein expression of the modified C5 gene is under control of rodent regulatory elements at the endogenous rodent C5 locus;   wherein the rodent cell is a mouse cell or a rat cell.   
     
     
         22 . The isolated rodent cell of  claim 21 , wherein the rodent cell is a rat cell. 
     
     
         23 . The isolated rodent cell of  claim 21 , wherein the rodent cell is a mouse cell. 
     
     
         24 . The isolated rodent cell of  claim 23 , wherein the modified C3 gene comprises exon 1 of the endogenous mouse C3 gene and exon 2 through exon 41 of the human C3 gene, and wherein expression of the modified C3 gene is under control of rodent regulatory elements at the endogenous rodent C3 locus. 
     
     
         25 . The isolated rodent cell of  claim 21 , wherein the human C3 gene sequence comprises exon 1 through exon 41 of the human C3 gene. 
     
     
         26 . An isolated rodent tissue, whose genome comprises
 (i) a replacement of a rodent C3 gene sequence at an endogenous rodent C3 locus with a human C3 gene sequence to form a modified C3 gene, wherein the rodent C3 gene sequence comprises an exon of the endogenous rodent C3 gene and the human C3 gene sequence comprises exon 2 through exon 41 of the human C3 gene;   (ii) a replacement of a rodent C5 gene sequence at an endogenous rodent C5 locus with a human C5 gene sequence to form a modified C5 gene, wherein the rodent C5 gene sequence comprises an exon of the endogenous rodent C5 gene and the human C5 gene sequence comprises exon 2 through exon 41 of the human C5 gene, wherein expression of the modified C5 gene is under control of rodent regulatory elements at the endogenous rodent C5 locus;   wherein the rodent tissue is a mouse tissue or a rat tissue.   
     
     
         27 . The isolated rodent tissue of  claim 26 , wherein the rodent tissue is a rat tissue. 
     
     
         28 . The isolated rodent tissue of  claim 26 , wherein the rodent tissue is a mouse tissue. 
     
     
         29 . The isolated rodent tissue of  claim 28 , wherein the modified C3 gene comprises exon 1 of the endogenous mouse C3 gene and exon 2 through exon 41 of the human C3 gene, and wherein expression of the modified C3 gene is under control of rodent regulatory elements at the endogenous rodent C3 locus. 
     
     
         30 . The isolated rodent tissue of  claim 26 , wherein the human C3 gene sequence comprises exon 1 through exon 41 of the human C3 gene. 
     
     
         31 . A rodent embryonic stem (ES) cell, whose genome comprises
 (i) a replacement of a rodent C3 gene sequence at an endogenous rodent C3 locus with a human C3 gene sequence to form a modified C3 gene, wherein the rodent C3 gene sequence comprises an exon of the endogenous rodent C3 gene and the human C3 gene sequence comprises exon 2 through exon 41 of the human C3 gene;   (ii) a replacement of a rodent C5 gene sequence at an endogenous rodent C5 locus with a human C5 gene sequence to form a modified C5 gene, wherein the rodent C5 gene sequence comprises an exon of the endogenous rodent C5 gene and the human C5 gene sequence comprises exon 2 through exon 41 of the human C5 gene, wherein expression of the modified C5 gene is under control of rodent regulatory elements at the endogenous rodent C5 locus;   wherein the rodent ES cell is a mouse ES cell or a rat ES cell.   
     
     
         32 . The rodent ES cell of  claim 31 , wherein the rodent ES cell is a rat ES cell. 
     
     
         33 . The rodent ES cell of  claim 31 , wherein the rodent ES cell is a mouse ES cell. 
     
     
         34 . The rodent ES cell of  claim 33 , wherein the modified C3 gene comprises exon 1 of the endogenous mouse C3 gene and exon 2 through exon 41 of the human C3 gene, and wherein expression of the modified C3 gene is under control of rodent regulatory elements at the endogenous rodent C3 locus. 
     
     
         35 . The rodent ES cell of  claim 31 , wherein the human C3 gene sequence comprises exon 1 through exon 41 of the human C3 gene. 
     
     
         36 . A rodent embryo comprising the rodent ES cell of  claim 31 , wherein the rodent embryo is a rat embryo or a mouse embryo. 
     
     
         37 . The rodent embryo of  claim 36 , wherein the rodent embryo is a rat embryo. 
     
     
         38 . The rodent embryo of  claim 36 , wherein the rodent embryo is a mouse embryo. 
     
     
         39 . The rodent embryo of  claim 38 , wherein the modified C3 gene comprises exon 1 of the endogenous mouse C3 gene and exon 2 through exon 41 of the human C3 gene, and wherein expression of the modified C3 gene is under control of rodent regulatory elements at the endogenous rodent C3 locus. 
     
     
         40 . The rodent embryo of  claim 36 , wherein the human C3 gene sequence comprises exon 1 through exon 41 of the human C3 gene.