{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T14:31:19Z","timestamp":1781620279573,"version":"3.54.5"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Human leukocyte antigen (HLA)\u2010DP is much less studied than other HLA class II antigens, that is, HLA\u2010DR and HLA\u2010DQ, etc. However, the accumulating data have suggested the important roles of DP\u2010restricted responses in the context of cancer, allergy, and infectious disease. Lack of animal models expressing these genes as authentic <jats:italic>cis<\/jats:italic>\u2010haplotypes blocks our understanding for the role of HLA\u2010DP haplotypes in immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To explore the potential <jats:italic>cis<\/jats:italic>\u2010acting control elements involved in the transcriptional regulation of the HLA\u2010DPA1\/DPB1 gene, we performed the expression analysis using bacterial artificial chromosome (BAC)\u2010based transgenic humanized mice in the C57BL\/6 background, which carried the entire HLA\u2010DP401 gene locus. We further developed a mouse model of <jats:italic>Staphylococcus aureus<\/jats:italic> pneumonia in HLA\u2010DP401 humanized transgenic mice, and performed the analysis on the expression pattern of HLA\u2010DP401 and immunological responses in the model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, we screened and identified a BAC clone spanning the entire HLA\u2010DP gene locus. DNA from this clone was analyzed for integrity by pulsed\u2010field gel electrophoresis and then microinjected into fertilized mouse oocytes to produce transgenic founder animals. Nine sets of PCR primers for regional markers with an average distance of 15\u00a0kb between each primer were used to confirm the integrity of the transgene in the five transgenic lines carrying the HLA\u2010DPA1\/DPB1 gene. Transgene copy numbers were determined by real\u2010time PCR analysis. HLA\u2010DP401 gene expression was analyzed at the mRNA and protein level. Although infection with <jats:italic>S aureus<\/jats:italic> Newman did not alter the percentage of immune cells in the spleen and thymus from the HLA\u2010DP401\u2010H2\u2010A\u03b21 humanized mice. Increased expression of HLA\u2010DP401 was observed in the thymus of the humanized mice infected by <jats:italic>S aureus<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We generated several BAC transgenic mice, and analyzed the expression of HLA\u2010DPA1\/DPB1 in those mice. A model of <jats:italic>S<\/jats:italic> <jats:italic>aureus<\/jats:italic>\u2010induced pneumonia in the HLA\u2010DP401\u2010H2\u2010A\u03b21<jats:sup>\u2212\/\u2212<\/jats:sup> humanized mice was further developed, and <jats:italic>S aureus<\/jats:italic> infection upregulated the HLA\u2010DP401 expression in thymus of those humanized mice. These findings demonstrate the potential of those HLA\u2010DPA1\/DPB1 transgenic humanized mice for developing animal models of infectious diseases and MHC\u2010associated immunological diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12158","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T07:19:51Z","timestamp":1616483991000},"page":"116-128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Generation and expression analysis of BAC humanized mice carrying HLA\u2010DP401 haplotype"],"prefix":"10.1002","volume":"4","author":[{"given":"Feng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Fudan Univeristy Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010min","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Laboratory 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