A transgenic rat with the human ATTR V30M: a novel tool for analyses of ATTR metabolisms.
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.
Ueda
Mitsuharu
M
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Ando
Yukio
Y
Hakamata
Yoji
Y
Nakamura
Masaaki
M
Yamashita
Taro
T
Obayashi
Konen
K
Himeno
Shingo
S
Inoue
Seiichiro
S
Sato
Yuki
Y
Kaneko
Takashi
T
Takamune
Nobutoki
N
Misumi
Shogo
S
Shoji
Shozo
S
Uchino
Makoto
M
Kobayashi
Eiji
E
D028227:Amyloid Neuropathies, Familial / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D004195:Disease Models, Animal; D006801:Humans; D016031:Liver Transplantation; D011228:Prealbumin / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods; D051381:Rats / Q000235:genetics* / Q000378:metabolism* / Q000601:surgery; D011994:Recombinant Proteins / Q000378:metabolism
D011228:Prealbumin; D011994:Recombinant Proteins