Humanized il-7 rodents

Abstract

Genetically modified non-human animals comprising a human or humanized interleukin-7 (IL-7) gene. Cells, embryos, and non-human animals comprising a human or humanized IL-7 gene. Rodents that express human or humanized IL-7 protein. Genetically modified mice that comprise a human or humanized IL-7-encoding gene in their germline, wherein the human or humanized IL-7-encoding gene is under control of endogenous mouse IL-7 regulatory sequences.

1 . An isolated cell obtained from a genetically modified rodent,
 wherein the genome of the cell and the genome of the rodent comprise a humanized IL-7 gene,   wherein the humanized IL-7 gene comprises exons 2, 3, 4, 5, and 6 of a human IL-7 gene, and is operably linked to endogenous rodent IL-7 5′ regulatory sequences,   wherein the human IL-7 gene comprises the nucleotide sequence of SEQ ID NO: 3,   wherein the rodent is a mouse or a rat, and   wherein the IL-7 protein encoded by the humanized IL-7 gene is expressed in the serum of the rodent.   
     
     
         2 . The cell of  claim 1 , wherein the humanized IL-7 gene is at an endogenous rodent IL-7 locus and comprises (i) exon 1 of an endogenous rodent IL-7 gene, and (ii) exons 2, 3, 4, 5, and 6 of the human IL-7 gene, and wherein the rodent IL-7 locus comprising the humanized IL-7 gene lacks rodent IL-7 exons 2, 3, 4, and 5. 
     
     
         3 . The cell of  claim 1 , wherein the humanized IL-7 gene comprises exon 1 of an endogenous rodent IL-7 gene, and exons 2, 3, 4, 5, and 6 of the human IL-7 gene. 
     
     
         4 . The cell of  claim 1 , wherein the rodent is a rat. 
     
     
         5 . The cell of  claim 1 , wherein the rodent is a mouse. 
     
     
         6 . An isolated tissue obtained from a genetically modified rodent,
 wherein the genome of the cells in the tissue and the genome of the rodent comprise a humanized IL-7 gene,   wherein the humanized IL-7 gene comprises exons 2, 3, 4, 5, and 6 of a human IL-7 gene, and is operably linked to endogenous rodent IL-7 5′ regulatory sequences,   wherein the human IL-7 gene comprises the nucleotide sequence of SEQ ID NO: 3,   wherein the rodent is a mouse or a rat, and   wherein the IL-7 protein encoded by the humanized IL-7 gene is expressed in the serum of the rodent.   
     
     
         7 . The tissue of  claim 6 , wherein the humanized IL-7 gene is at an endogenous rodent IL-7 locus and comprises (i) exon 1 of an endogenous rodent IL-7 gene, and (ii) exons 2, 3, 4, 5, and 6 of the human gene, and wherein the rodent IL-7 locus comprising the humanized IL-7 gene lacks rodent IL-7 exons 2, 3, 4, and 5. 
     
     
         8 . The tissue of  claim 6 , wherein the humanized IL-7 gene comprises exon 1 of an endogenous rodent IL-7 gene, and exons 2, 3, 4, 5, and 6 of the human IL-7 gene. 
     
     
         9 . The tissue of  claim 6 , wherein the rodent is a rat. 
     
     
         10 . The tissue of  claim 6 , wherein the rodent is a mouse. 
     
     
         11 . An isolated rodent embryonic stem (ES) cell whose genome comprises a humanized IL-7 gene,
 wherein the humanized IL-7 gene comprises exons 2, 3, 4, 5, and 6 of a human IL-7 gene, and is operably linked to endogenous rodent IL-7 5′ regulatory sequences,   wherein the human IL-7 gene comprises the nucleotide sequence of SEQ ID NO: 3,   wherein the embryonic stem cells generates a rodent whose genome comprises said humanized IL-7 gene,   wherein the rodent is a mouse or a rat and expresses the IL-7 protein encoded by the humanized IL-7 gene in the serum.   
     
     
         12 . The ES cell of  claim 11 , wherein the humanized IL-7 gene is at an endogenous rodent IL-7 locus and comprises (i) exon 1 of an endogenous rodent IL-7 gene, and (ii) exons 2, 3, 4, 5, and 6 of the human IL-7 gene, and wherein the rodent IL-7 locus comprising the humanized IL-7 gene lacks rodent IL-7 exons 2, 3, 4, and 5. 
     
     
         13 . The ES cell of  claim 11 , wherein the humanized IL-7 gene comprises exon 1 of an endogenous rodent IL-7 gene, and exons 2, 3, 4, 5, and 6 of the human IL-7 gene. 
     
     
         14 . The ES cell of  claim 11 , wherein the rodent is a rat. 
     
     
         15 . The ES cell of  claim 11 , wherein the rodent is a mouse. 
     
     
         16 . A rodent embryo comprising the rodent ES cell of  claim 11 . 
     
     
         17 . The rodent embryo of  claim 16 , wherein the humanized IL-7 gene is at an endogenous rodent IL-7 locus and comprises (i) exon 1 of an endogenous rodent IL-7 gene, and (ii) exons 2, 3, 4, 5, and 6 of the human IL-7 gene, and wherein the rodent IL-7 locus comprising the humanized IL-7 gene lacks rodent IL-7 exons 2, 3, 4, and 5. 
     
     
         18 . The rodent embryo of  claim 16 , wherein the humanized IL-7 gene comprises exon 1 of an endogenous rodent IL-7 gene, and exons 2, 3, 4, 5, and 6 of the human IL-7 gene. 
     
     
         19 . The rodent embryo of  claim 16 , wherein the rodent embryo is a rat embryo. 
     
     
         20 . The rodent embryo of  claim 16 , wherein the rodent embryo is a mouse embryo.