HUMANIZED IL-4 AND IL-4Ra ANIMALS

A triply humanized mouse, comprising (i) a replacement of a genomic DNA of a mouse IL-4Rα gene at an endogenous mouse IL-4Rα locus with a human genomic DNA of a human IL-4Rα gene to form a humanized IL-4Rα gene, wherein the genomic DNA of the mouse IL-4Rα gene comprises the ATG initiation codon of exon 1 through exon 5 of the mouse IL-4Rα gene, and the human genomic DNA of the human IL-4Rα gene comprises the ATG initiation codon of exon 1 through exon 5 of the human IL-4Rα gene, wherein the humanized IL-4Rα gene comprises the ATG initiation codon of exon 1 through exon 5 of the human IL-4Rα gene and exons 6-9 of the mouse IL-4Rα gene, wherein expression of the humanized IL-4Rα gene is under control of the mouse IL-4Rα promoter at the endogenous mouse IL-4Rα locus,

• (ii) a replacement of a genomic DNA of a mouse IL-4 gene at an endogenous mouse IL-4 locus with a genomic DNA of a human IL-4 gene to form a humanized IL-4 gene, wherein the genomic DNA of the mouse IL-4 gene comprises the ATG initiation codon of exon 1 through exon 4 of the mouse IL-4 gene, and the genomic DNA of the human IL-4 gene comprises the ATG initiation codon of exon 1 through exon 4 of the human IL-4 gene, and wherein expression of the humanized IL-4 gene is under control of the mouse IL-4 promoter at the endogenous mouse IL-4 locus, and
• (iii) a replacement of a genomic DNA of a mouse IL-33 gene at an endogenous mouse IL-33 locus with a genomic DNA of a human IL-33 gene such that the locus encodes a human IL-33 but not mouse IL-33.

A mouse embryonic stem cell, comprising

• (i) a replacement of a genomic DNA of a mouse IL-4Rα gene at an endogenous mouse IL-4Rα locus with a human genomic DNA of a human IL-4Rα gene to form a humanized IL-4Rα gene, wherein the genomic DNA of the mouse IL-4Rα gene comprises the ATG initiation codon of exon 1 through exon 5 of the mouse IL-4Rα gene, and the human genomic DNA of the human IL-4Rα gene comprises the ATG initiation codon of exon 1 through exon 5 of the human IL-4Rα gene, wherein the humanized IL-4Rα gene comprises the ATG initiation codon of exon 1 through exon 5 of the human IL-4Rα gene and exons 6-9 of the mouse IL-4Rα gene, wherein expression of the humanized IL-4Rα gene is under control of the mouse IL-4Rα promoter at the endogenous mouse IL-4Rα locus,
• (ii) a replacement of a genomic DNA of a mouse IL-4 gene at an endogenous mouse IL-4 locus with a genomic DNA of a human IL-4 gene to form a humanized IL-4 gene, wherein the genomic DNA of the mouse IL-4 gene comprises the ATG initiation codon of exon 1 through exon 4 of the mouse IL-4 gene, and the genomic DNA of the human IL-4 gene comprises the ATG initiation codon of exon 1 through exon 4 of the human IL-4 gene, and wherein expression of the humanized IL-4 gene is under control of the mouse IL-4 promoter at the endogenous mouse IL-4 locus, and
• (iii) a replacement of a genomic DNA of a mouse IL-33 gene at an endogenous mouse IL-33 locus with a genomic DNA of a human IL-33 gene such that the locus encodes a human IL-33 but not mouse IL-33.