Anti-endoglin antibodies and knockin mice expressing novel human/mouse chimeric endoglin

Abstract

Provided are compositions and methods that relate to prophylaxis and therapy of angiogenesis associated disease and includes novel knockin mice which express novel human/mouse chimeric endoglin, vectors for use in making such mice, and murine embryonic stem cells comprising the novel human/mouse transgene. Also provided are anti-human endoglin monoclonal antibodies (mAbs) which can be used as antiangiogenic agents for prophylaxis or therapy of human tumor angiogenesis and human angiogenesis-associated diseases having excessive vascularization. The mAbs do not cross react with murine endoglin. Also provides are methods for using the anti-human endoglin mAbs for prophylaxis or therapy of human tumor angiogenesis and for angiogenesis-associated diseases having excessive vascularization.

What is claimed is: 
     
         1 . A recombinant vector comprising human endoglin (hENG) exons selected from hENG exons 4, 5, 6, 7 and 8, and combinations thereof, wherein the vector is suitable for use in homologous replacement of a homologous region of the murine endoglin gene. 
     
     
         2 . The recombinant vector of  claim 1 , wherein the recombinant vector comprises exons 4, 5, 6, 7 and 8 of the hENG gene. 
     
     
         3 . The recombinant vector of  claim 1 , wherein the recombinant vector comprises one or more regions of sequence which are identical to a murine endoglin gene sequence. 
     
     
         4 . A murine embryonic stem cell comprising a replacement of murine endoglin gene exons selected from the group consisting of murine endoglin gene exons 4, 5, 6, 7, and 8, and combinations thereof, and wherein the murine endoglin exons are replaced with homologous human endoglin exons. 
     
     
         5 . The murine embryonic stem cell of  claim 4 , wherein the murine endoglin exons 5 and 6 are replaced with human endoglin exons 5 and 6, respectively. 
     
     
         6 . The murine embryonic stem cell of  claim 4 , wherein the murine endoglin exons 4, 5, 6, 7, and 8 are replaced with human endoglin exons 4, 5, 6, 7, and 8, respectively.