Amyloid deposition in a mouse m transthyretin and retinol-binding

Familial amyloidotic polyneuropathy is an autosom (TTR) gene. The process of TTR amyloidogenesis be stabilizers, such as Tafamidis and Diflunisal, are now these drugs. Although several mouse models have associates with mouse RBP4, resulting in different overcome this problem, we previously produced hu Ttr, and Rbp4). By mating these mice Rbp4 and Ttr:Rbp4 (Ttr:Tg[6.0hTTRMet30]) or knockout Ttr backg humanized mouse showed 1/25 of serum hTTR and pronounced in Ttr:Rbp4 than of amyloid deposition was also observed in Ttr gene. Furthermore, amyloid deposition was first obs strains, anti-TTR antibody-positive deposits were deposition. In double-humanized mice, gel filtratio suggesting importance of free TTR for amyloid dep Xiangshun Li and Yanyi Lyu contributed equally to this wor * Shoude Jin jinshoude@163.com * Zhenghua Li lizhenghua@hrbmu.edu.cn liseika@kumamoto-u.ac.jp 1 Division of Respiratory Disease, The Fourth Affiliated Ho Harbin Medical University, Harbin, China 2 Department of Histology and Embryology, Harbin Medic University, Harbin, China 3 Yamamura Project Laboratory, Institute of Resource Deve and Analysis, Kumamoto University, Kumamoto, Japan 4 Department of Developmental Genetics, Institute of Reso Development and Analysis, Kumamoto University, Kumamoto, Japan 5 Research and Development, Chiesi Farmaceutici, Parma, 12 34 56 78 90 () ;,: odel humanized at the protein 4 loci shuang Mu ● Lixia Qiang ● Li Liu ● Kimi Araki ● de Jin ● Zhenghua Li pted: 2 December 2017 al dominant disorder caused by a point mutation in the transthyretin gins with rate-limiting dissociation of the TTR tetramer. Thus, the TTR in clinical trials. Mouse models will be useful to testing the efficacy of been generated, they all express mouse Rbp4. Thus, human TTR kinetic and thermodynamic stability profiles of TTR tetramers. To manized mouse strains at both the TTR and Rbp4 loci (Ttr, , we produced double-humanized mouse strains, Ttr: . We used conventional transgenic mouse strains on a wild-type round (Ttr:Tg[6.0hTTRMet30]) as reference strains. The double1/40 of serum hRBP4 levels. However, amyloid deposition was more in conventional transgenic mouse strains. In addition, a similar amount 30/ :Rbp4 hRBP4 mice that carried the wild-type human TTR erved in the sciatic nerve without any additional genetic change. In all found in earlier age and at higher percentage than amyloid fibril n analysis of serum revealed that most hTTR was free of hRBP4, osition.