Mouse having a humanized b-cell activating factor gene

A targeting nucleic acid vector, comprising

• a 5′ homology arm comprising a mouse genomic sequence upstream of exon 1 of a mouse B-cell Activating Factor (Baff) gene and exon 1 and exon 2 of the mouse Baff gene,
• a human genomic DNA fragment comprising exons 3-6 of a human BAFF gene,
• a drug selection cassette, and
• a 3′ homology arm comprising a mouse genomic sequence comprising a part of exon 7 of
• the mouse Baff gene that includes 3′ UTR and polyadenylation site,
• wherein the 5′ and 3′ homology arms are capable of mediating integration of the human genomic fragment into a mouse Baff locus which results in a replacement of a mouse genomic fragment comprising exon 3-6 and a part of exon 7 of the mouse Baff gene to form a humanized Baff gene,
• wherein the coding exons of the humanized Baff gene consist of exons 1-2 of the mouse Baff gene and exons 3-6 of the human BAFF gene,
• wherein the humanized Baff gene is under control of the mouse Baff promoter at the mouse Baff locus and encodes a humanized Baff protein comprising an extracellular portion of the human BAFF protein linked to an intracellular portion of the mouse Baff protein encoded by the mouse Baff gene, and
• wherein the extracellular portion of the human BAFF protein is at least 98% identical to the amino acid sequence as set forth in amino acids 142 to 285 of SEQ ID NO:
• 5.