Generating a transgenic mouse line stably expressing human MHC surface antigen from a HAC carrying multiple genomic BACs

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• 作者：Yoshinori Hasegawa (1) (2)
  Tomoyuki Ishikura (3)
  Takanori Hasegawa (3)
  Takashi Watanabe (3)
  Junpei Suzuki (2)
  Manabu Nakayama (2)
  Yoshiaki Okamura (1)
  Tuneko Okazaki (4)
  Haruhiko Koseki (3)
  Osamu Ohara (2) (3)
  Masashi Ikeno (4)
  Hiroshi Masumoto (1)
  
  1. Laboratory of Cell Engineering ; Department of Frontier Research ; Kazusa DNA Research Institute ; 2-6-7 Kazusa-Kamatari ; Kisarazu ; Chiba ; 292-0818 ; Japan
  2. Department of Technology Development ; Kazusa DNA Research Institute ; 2-6-7 Kazusa-Kamatari ; Kisarazu ; Chiba ; 292-0818 ; Japan
  3. RIKEN Center for Integrative Medical Sciences (IMS-RCAI) ; 1-7-22 Suehiro-cho Tsurumi-ku ; Yokohama ; Kanagawa ; 230-0045 ; Japan
  4. Chromo Research Inc. ; 1212 Shihongi ; Midori-ku ; Nagoya ; Aichi ; 458-0039 ; Japan
  
• 刊名：Chromosoma
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：124
• 期：1
• 页码：107-118
• 全文大小：3,016 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Developmental Biology
  Biochemistry
  Human Genetics
  Animal Genetics and Genomics
  Eukaryotic Microbiology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0886

文摘

The human artificial chromosome (HAC) vector is a promising tool to improve the problematic suppression and position effects of transgene expression frequently seen in transgenic cells and animals produced by conventional plasmid or viral vectors. We generated transgenic mice maintaining a single HAC vector carrying two genomic bacterial artificial chromosomes (BACs) from human HLA-DR loci (DRA and DRB1). Both transgenes on the HAC in transgenic mice exhibited tissue-specific expression in kidney, liver, lung, spleen, lymph node, bone marrow, and thymus cells in RT-PCR analysis. Stable functional expression of a cell surface HLA-DR marker from both transgenes, DRA and DRB1 on the HAC, was detected by flow cytometric analysis of splenocytes and maintained through at least eight filial generations. These results indicate that the de novo HAC system can allow us to manipulate multiple BAC transgenes with coordinated expression as a surface antigen through the generation of transgenic animals.