Tissue specific expression of exogenous proteins in transgenic chickens

Abstract

Transgenes encoding exogenous proteins are stably integrated into embryonic stem cells and are present in the somatic tissue of transgenic or chimeric birds. The transgenes encode exogenous proteins and are expressed in any of endodermal, ectodermal, mesodermal, or extra embryonic tissue. Tissue specificity is provided by selecting the content of the transgene accordingly. Transgenic birds whose genome is comprised of trangene derived exogenous DNA express exogenous proteins with tissue specificity, and specifically express exogenous proteins in the tubular gland cells of the oviduct to concentrate exogenous proteins in egg white.

1 . A chicken selectively expressing exogenous protein in tubular gland cells wherein the protein is encoded by a transgene stably integrated into a genome of the chicken and wherein the transgene is comprised at least a portion of a promoter of a gene encoding an egg white protein that is operably linked to DNA encoding the exogenous protein.  
   
   
       2 . The chicken of  claim 1  further comprising at least a second portion of a promoter of a gene encoding an egg white protein flanking the 3′ end of the DNA encoding the exogenous protein.  
   
   
       3 . The chicken of  claim 1  wherein the exogenous protein is a monoclonal antibody.  
   
   
       4 . The chicken of  claim 3  wherein the monoclonal antibody is comprised of a human heavy chain.  
   
   
       5 . The chicken of  claim 4  wherein the monoclonal antibody is isotype IgG.  
   
   
       6 . The chicken of  claim 1  wherein the egg white protein is ovalbumin.  
   
   
       7 . The chicken of  claim 1  wherein the egg white protein is selected from the group consisting of ovotransferrin, ovomucoid, lysozyme, ovoglobulin G2, ovoglobulin G3, ovoinhibitor, cystatin, ovoglycoprotein, ovoflavoprotein, ovomacroglobulin, and avidin.  
   
   
       8 . The chicken of  claim 1  wherein the size of the transgene is greater than 15 kb.  
   
   
       9 . A chicken egg containing a human protein in the egg white, wherein the human protein is encoded by a transgene stable integrated into the genome of a transgene chicken.  
   
   
       10 . The egg of  claim 9  wherein the human protein is a monoclonal antibody.  
   
   
       11 . A vector comprising a promoter linked to a heterologous coding sequence to express said coding sequence in tubular gland cells of an avian oviduct.  
   
   
       12 . The vector of  claim 11 , wherein said promoter is selected from the group consisting of an ovomucoid, ovalbumin, lysozyme, and ovomucin promoter.  
   
   
       13 . The vector of  claim 11 , further comprising a gene encoding a selectable marker.  
   
   
       14 . The vector of  claim 11 , further comprising an internal ribosome entry site element.  
   
   
       15 . The vector of  claim 11 , wherein the heterologous coding sequence encodes a human antibody.