Cell Res:吉林大学诞生世界首例ROSA26基因打靶猪

2014-02-21 佚名 吉林大学

吉林大学动物医学学院院长、中科院广州生物医药与健康研究院研究员赖良学博士与美国密西根大学王忠教授合作,获得了世界首例ROSA26定点基因敲入猪模型。利用该模型猪,成功地实现重组酶介导的基因交换,从而解决了一直困扰转基因猪研究领域的效率低下、表型不确定的问题,该成果的获得将极大地推动转基因猪在农业和医学方面的应用。研究成果于2月7日在线发表在国际著名期刊Cell Research。

吉林大学动物医学学院院长、中科院广州生物医药与健康研究院研究员赖良学博士与美国密西根大学王忠教授合作,获得了世界首例ROSA26定点基因敲入猪模型。利用该模型猪,成功地实现重组酶介导的基因交换,从而解决了一直困扰转基因猪研究领域的效率低下、表型不确定的问题,该成果的获得将极大地推动转基因猪在农业和医学方面的应用。研究成果于2月7日在线发表在国际著名期刊Cell Research。【原文下载】


转基因猪在农业新品种培育和生物医药研究中具有非常重要的应用价值。长期以来由于缺乏猪胚胎干细胞,转基因猪的制备主要依赖于体细胞基因修饰和体细胞核移植技术。目前对体细胞的基因修饰主要通过将外源基因随机插入猪基因组,因此外源基因在猪基因组中的整合位点和拷贝数不可控,从而导致外源基因猪体内表达不稳定,转基因猪个体之间表型不均一,因此限制了转基因猪的培育与应用。

本研究团队首先在猪基因组中找到了一个特殊基因位点:ROSA26,处在这个位点后的基因会广泛表达于所有组织和细胞中。在过去的20年中,通过对小鼠Rosa26基因位点的修饰,获得了一系列Rosa26小鼠模型,并在发育生物学以及干细胞研究中发挥了巨大的作用,目前该位点仅在人胚胎干细胞和大鼠中被鉴定和修饰,尚未在大动物中发现及应用。

研究人员利用TALEN介导的基因敲入技术,成功地构建了世界上第一个ROSA26定点敲入Cre重组酶报告基因的大动物模型。该动物模型将可在猪体内世系追踪各类干细胞的分化和再生,为揭示和人类干细胞相关的疾病机理和实施干细胞治疗提供宝贵的大动物实验依据。

在此基础上,研究人员李小平及合作者巧妙设计,在ROSA26位点引入一对异源loxp位点,经重组酶介导的基因交换,成功将EGFP基因替换为红色荧光蛋白tdTomato基因,由此又获得了世界上第一个重组酶介导的基因交换大动物模型。利用该模型,研究人员可以将任意基因通过重组酶介导的基因交换插入到ROSA26位点,实现目的基因在大动物所有组织中的无差异表达。同时由于重组酶介导的基因交换无需药物筛选即可获得,从而使获得的转基因猪不携带外源的药物抗性基因,可去除转基因猪农产品的生物安全和食品安全隐患。

该研究获国家科技部“重大基础研究计划”和美国国家健康研究院(NIH)资助。

原始出处:
Li X1, Yang Y1, Bu L2, Guo X3, Tang C1, Song J4, Fan N3, Zhao B3, Ouyang Z3, Liu Z3, Zhao Y3, Yi X3, Quan L1, Liu S1, Yang Z1, Ouyang H1, Chen YE5, Wang Z5, Lai L6.Rosa26-targeted swine models for stable gene over-expression and Cre-mediated lineage tracing.Cell Res. 2014 Feb 7. doi: 10.1038/cr.2014.15. 【原文下载】

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    2014-03-12 维他命
  5. [GetPortalCommentsPageByObjectIdResponse(id=1968422, encodeId=868a19684228e, content=<a href='/topic/show?id=a57f208660f' target=_blank style='color:#2F92EE;'>#世界首例#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20866, encryptionId=a57f208660f, topicName=世界首例)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=917c196, createdName=sjzlzc007, createdTime=Sun Apr 20 20:18:00 CST 2014, time=2014-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1992135, encodeId=d876199213519, content=<a href='/topic/show?id=a32341e4699' target=_blank style='color:#2F92EE;'>#基因打靶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41746, encryptionId=a32341e4699, topicName=基因打靶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Fri May 09 18:18:00 CST 2014, time=2014-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1868776, encodeId=6de81868e76c3, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Feb 02 00:18:00 CST 2015, time=2015-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959018, encodeId=0b111959018ef, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Mar 12 21:18:00 CST 2014, time=2014-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1349734, encodeId=c9f71349e344c, content=<a href='/topic/show?id=3d0d134904c' target=_blank style='color:#2F92EE;'>#OSA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13490, encryptionId=3d0d134904c, topicName=OSA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=322359, createdName=bioon3, createdTime=Sun Feb 23 06:18:00 CST 2014, time=2014-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1363942, encodeId=03b61363942d5, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Sun Feb 23 06:18:00 CST 2014, time=2014-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555210, encodeId=d9221555210ba, content=<a href='/topic/show?id=f367681e434' target=_blank style='color:#2F92EE;'>#猪#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68174, encryptionId=f367681e434, topicName=猪)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ec214601917, createdName=muzishouyi, createdTime=Sun Feb 23 06:18:00 CST 2014, time=2014-02-23, status=1, ipAttribution=)]
    2014-02-23 bioon3
  6. [GetPortalCommentsPageByObjectIdResponse(id=1968422, encodeId=868a19684228e, content=<a href='/topic/show?id=a57f208660f' target=_blank style='color:#2F92EE;'>#世界首例#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20866, encryptionId=a57f208660f, topicName=世界首例)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=917c196, createdName=sjzlzc007, createdTime=Sun Apr 20 20:18:00 CST 2014, time=2014-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1992135, encodeId=d876199213519, content=<a href='/topic/show?id=a32341e4699' target=_blank style='color:#2F92EE;'>#基因打靶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41746, encryptionId=a32341e4699, topicName=基因打靶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Fri May 09 18:18:00 CST 2014, time=2014-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1868776, encodeId=6de81868e76c3, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Feb 02 00:18:00 CST 2015, time=2015-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959018, encodeId=0b111959018ef, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Mar 12 21:18:00 CST 2014, time=2014-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1349734, encodeId=c9f71349e344c, content=<a href='/topic/show?id=3d0d134904c' target=_blank style='color:#2F92EE;'>#OSA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13490, encryptionId=3d0d134904c, topicName=OSA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=322359, createdName=bioon3, createdTime=Sun Feb 23 06:18:00 CST 2014, time=2014-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1363942, encodeId=03b61363942d5, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Sun Feb 23 06:18:00 CST 2014, time=2014-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555210, encodeId=d9221555210ba, content=<a href='/topic/show?id=f367681e434' target=_blank style='color:#2F92EE;'>#猪#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68174, encryptionId=f367681e434, topicName=猪)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ec214601917, createdName=muzishouyi, createdTime=Sun Feb 23 06:18:00 CST 2014, time=2014-02-23, status=1, ipAttribution=)]
    2014-02-23 lsndxfj
  7. [GetPortalCommentsPageByObjectIdResponse(id=1968422, encodeId=868a19684228e, content=<a href='/topic/show?id=a57f208660f' target=_blank style='color:#2F92EE;'>#世界首例#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20866, encryptionId=a57f208660f, topicName=世界首例)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=917c196, createdName=sjzlzc007, createdTime=Sun Apr 20 20:18:00 CST 2014, time=2014-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1992135, encodeId=d876199213519, content=<a href='/topic/show?id=a32341e4699' target=_blank style='color:#2F92EE;'>#基因打靶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41746, encryptionId=a32341e4699, topicName=基因打靶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Fri May 09 18:18:00 CST 2014, time=2014-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1868776, encodeId=6de81868e76c3, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Feb 02 00:18:00 CST 2015, time=2015-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959018, encodeId=0b111959018ef, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Mar 12 21:18:00 CST 2014, time=2014-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1349734, encodeId=c9f71349e344c, content=<a href='/topic/show?id=3d0d134904c' target=_blank style='color:#2F92EE;'>#OSA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13490, encryptionId=3d0d134904c, topicName=OSA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=322359, createdName=bioon3, createdTime=Sun Feb 23 06:18:00 CST 2014, time=2014-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1363942, encodeId=03b61363942d5, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Sun Feb 23 06:18:00 CST 2014, time=2014-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555210, encodeId=d9221555210ba, content=<a href='/topic/show?id=f367681e434' target=_blank style='color:#2F92EE;'>#猪#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68174, encryptionId=f367681e434, topicName=猪)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ec214601917, createdName=muzishouyi, createdTime=Sun Feb 23 06:18:00 CST 2014, time=2014-02-23, status=1, ipAttribution=)]
    2014-02-23 muzishouyi