A transgenic rat with the human ATTR V30M: a novel tool for analyses of ATTR metabolisms.
A transgenic rat with the human ATTR V30M: a novel tool for analyses of ATTR metabolisms.
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DOI：
10.1016/j.bbrc.2006.11.045
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发表时间：
2007-01
影响因子：
3.1
通讯作者：
M. Ueda;Y. Ando;Y. Hakamata;Masaaki Nakamura;T. Yamashita;K. Obayashi;S. Himeno;Seiichiro Inoue;Yuki Sato;Takashi Kaneko;N. Takamune;S. Misumi;S. Shoji;M. Uchino;E. Kobayashi
中科院分区：
文献类型：
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作者：
M. Ueda;Y. Ando;Y. Hakamata;Masaaki Nakamura;T. Yamashita;K. Obayashi;S. Himeno;Seiichiro Inoue;Yuki Sato;Takashi Kaneko;N. Takamune;S. Misumi;S. Shoji;M. Uchino;E. Kobayashi
淀粉样甲状腺素运载蛋白（ATTR）是家族性淀粉样多发性神经病（FAP）的致病蛋白。为了建立用于分析包括肝移植后的ATTR代谢的工具，我们开发了表达人ATTR V30 M的转基因大鼠模型，并证实了人ATTR V30 M在各种组织中的表达。对纯化的TTR的质谱分析显示，大鼠内源性TTR和人ATTR V30 M形成四聚体。刚果红染色和免疫组化显示，在转基因大鼠的胃肠道中检测到人ATTR V30 M的非纤维状沉积，但未检测到淀粉样沉积。在肝移植后24小时，接受正常大鼠肝脏的转基因大鼠中的血清人ATTR V30 M水平变得低于可检测水平。因此，这些结果表明，这种转基因大鼠可能是一个有用的动物模型，分析人类ATTR V30 M的代谢，包括肝移植研究。
Amyloidogenic transthyretin (ATTR) is the pathogenic protein of familial amyloidotic polyneuropathy (FAP). To establish a tool for analyses of ATTR metabolisms including after liver transplantations, we developed a transgenic rat model expressing human ATTR V30M and confirmed expressions of human ATTR V30M in various tissues. Mass spectrometry for purified TTR revealed that rat intrinsic TTR and human ATTR V30M formed tetramers. Congo red staining and immunohistochemistry revealed that nonfibrillar deposits of human ATTR V30M, but not amyloid deposits, were detected in the gastrointestinal tracts of the transgenic rats. At 24h after liver transplantation, serum human ATTR V30M levels in transgenic rats that received livers from normal rats became lower than detectable levels. These results thus suggest that this transgenic rat may be a useful animal model which analyzes the metabolism of human ATTR V30M including liver transplantation studies.