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.

What is claimed is: 
     
         1 . A genetically modified rodent cell whose genome comprises a humanized IL-7 gene, wherein the humanized IL-7 gene comprises human IL-7 exons 2, 3, 4, 5, and 6, and is operably linked to endogenous rodent IL-7 5′ regulatory sequences, and wherein the rodent cell is a rat cell or a mouse cell. 
     
     
         2 . The genetically modified rodent cell of  claim 1 , wherein the humanized IL-7 gene is at an endogenous rodent IL-7 locus, and the rodent IL-7 locus comprising the humanized IL-7 gene lacks rodent IL-7 exons 2, 3, 4 and 5. 
     
     
         3 . The genetically modified rodent cell of  claim 1 , wherein the humanized IL-7 gene comprises rodent IL-7 exon 1, and human IL-7 exons 2, 3, 4, 5, and 6. 
     
     
         4 . The genetically modified rodent cell of  claim 1 , wherein the rodent cell is a rat cell. 
     
     
         5 . The genetically modified rodent cell of  claim 1 , wherein the rodent cell is a mouse cell. 
     
     
         6 . The genetically modified rodent cell of  claim 1 , wherein the rodent cell is an embryonic stem (ES) cell. 
     
     
         7 . The genetically modified rodent cell of  claim 1 , wherein the rodent cell secretes the IL-7 protein encoded by the humanized IL-7 gene. 
     
     
         8 . A rodent embryo comprising at least one rodent donor cell whose genome comprises a humanized IL-7 gene, wherein the humanized IL-7 gene comprises human IL-7 exons 2, 3, 4, 5, and 6, and is operably linked to endogenous rodent IL-7 5′ regulatory sequences, and wherein the rodent embryo is a rat embryo or a mouse embryo. 
     
     
         9 . The rodent embryo of  claim 8 , wherein the humanized IL-7 gene is at an endogenous rodent IL-7 locus, and the rodent IL-7 locus comprising the humanized IL-7 gene lacks rodent IL-7 exons 2, 3, 4 and 5. 
     
     
         10 . The rodent embryo of  claim 8 , wherein the humanized IL-7 gene comprises rodent IL-7 exon 1, and human IL-7 exons 2, 3, 4, 5, and 6. 
     
     
         11 . The rodent embryo of  claim 8 , wherein the rodent embryo is a rat embryo. 
     
     
         12 . The rodent embryo of  claim 8 , wherein the rodent embryo is a mouse embryo. 
     
     
         13 . The rodent embryo of  claim 8 , wherein the rodent donor cell is a rodent embryonic stem (ES) cell. 
     
     
         14 . A tissue of a genetically modified rodent, wherein the rodent comprises in its germline a humanized IL-7 gene, wherein the humanized IL-7 gene comprises human IL-7 exons 2, 3, 4, 5, and 6, and is operably linked to endogenous rodent IL-7 5′ regulatory sequences, and wherein the rodent selected from a rat and a mouse. 
     
     
         15 . The tissue of  claim 14 , wherein the humanized IL-7 gene is at an endogenous rodent IL-7 locus, and the rodent IL-7 locus comprising the humanized IL-7 gene lacks rodent IL-7 exons 2, 3, 4 and 5. 
     
     
         16 . The tissue of  claim 14 , wherein the humanized IL-7 gene comprises rodent IL-7 exon 1, and human IL-7 exons 2, 3, 4, 5, and 6. 
     
     
         17 . The tissue of  claim 14 , wherein the rodent is a rat. 
     
     
         18 . The tissue of  claim 14 , wherein the rodent is a mouse. 
     
     
         19 . The tissue of  claim 14 , wherein the tissue is selected from the group consisting of thymic, splenic, epidermal and intestinal tissue. 
     
     
         20 . A DNA construct, comprising from 5′ to 3′,
 a nucleic acid sequence homologous to a mouse IL-7 5′ non-coding sequence; 
 a human genomic sequence comprises human IL-7 exons 2, 3, 4, 5, and 6, 
 wherein the human genomic sequence does not include a human IL-7 5′ regulatory sequence; and 
 a nucleic acid sequence homologous to a mouse IL-7 3′ non-coding sequence. 
 
     
     
         21 . The DNA construct of  claim 20 , wherein the nucleic acid sequence homologous to a mouse IL-7 5′ non-coding sequence comprises a region of homology to a mouse IL-7 exon 1 sequence.