title: A transgenic rat with the human ATTR V30M: a novel tool for analyses of ATTR metabolisms.
abstract: 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.
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hakamata
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.forename: Shingo
authors.initials: S
authors.lastname: Himeno
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Inoue
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Nobutoki
authors.initials: N
authors.lastname: Takamune
authors.forename: Shogo
authors.initials: S
authors.lastname: Misumi
authors.forename: Shozo
authors.initials: S
authors.lastname: Shoji
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchino
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
mesh_terms: 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
chemical_list: D011228:Prealbumin; D011994:Recombinant Proteins