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Using a plasmid-mediated gene targeting strategy, a congenic C57BL/6 mouse was developed by replacing mouse Dpp4 exons 10–12 with the corresponding human DPP4 codons (hDPP4-KI). For the studies reported, we used mice homozygous for hDPP4.A congenic C57BL/6 mouse with mouse Dpp4 exons 10–12 replaced with the human DPP4 codons was generated by Taconic Biosciences.This change in exoncoding sequence allowed the modified mouse gene product to display amino acids required for virus binding (18–20). The targeting strategy was based on National Center for Biotechnology Information transcripts NM_010074_3 (mouse) and NM_001935_3 (human). The targeting vector was generated using BAC clones from the mouse C57BL/6J RPCIB-731 and human RPCIB-753 BAC libraries. Mouse genomic sequence from codon I264 in exon 10 to codon V340 in exon 12 was replaced with its human counterpart.. Human DPP4 KI mice were anesthetized with ketamine/xylazine (87.5 mg/kg ketamine/12.5 mg/kg xylazine) and infected intranasally with MERS-CoV in 50 μL DMEM.

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