hDPP4(2) Mouse

The DPP4 gene (CD26) encodes dipeptidyl peptidase 4, an intrinsic type II transmembrane glycoprotein and a serine exopeptidase involved in glucose and insulin metabolism and immune regulation. The DPP4 protein is a functional receptor for the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The spike protein of MERS-CoV binds to DPP4, mediating the virus's attachment to host cells and promoting virus-cell fusion, thereby initiating infection ^[1-2]. Studies have found that the DPP4 protein may interact with the S1 domain of the spike glycoprotein of COVID-19, aiding in enhancing the transmission efficiency of viral particles ^[3]. Experimental evidence has shown that hDPP4 transgenic mice infected with MERS-CoV experience high mortality and severe pneumonia ^[4]. These mice infected with Manis javanica HKU4-related coronavirus (MjHKU4r-CoV-1) develop mild to moderate pulmonary histological damage ^[5]. Thus, gene-edited mice expressing human DPP4 protein are important tools for studying coronavirus infections. Additionally, DPP4 expression is severely dysregulated in diseases such as inflammation, cancer, obesity, and diabetes. DPP4 is highly expressed in the intestine, where it selectively cleaves N-terminal dipeptides from various substrates, including incretins, to inactivate multiple bioactive peptides. Since incretins like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are crucial for regulating postprandial insulin secretion, inhibiting DPP4 to elevate endogenous GLP-1 and GIP levels to increase insulin levels has become an important treatment method for type 2 diabetes (T2D) ^[6].

The hDPP4(2) mouse is a humanized model constructed by gene editing technology to replace a partial region of the mouse Dpp4 gene with the human DPP4 gene CDS sequence. This model can be used to study the infection mechanisms of viruses such as MERS-CoV and COVID-19, as well as to develop related virus vaccines. Additionally, this model can be utilized to develop DPP4 inhibitor therapies. Similar models include the hDPP4 mouse (Catalog ID: I001187), constructed on the C57BL/6NCya background strain, which replaces the sequence of the mouse Dpp4 gene with the human DPP4 gene CDS sequence, and the hDPP4(BALB/c) mouse (Catalog ID: I001189), constructed on the BALB/cAnCya background strain. These models meet the experimental needs of different strain backgrounds.