Aki Sugano
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Publications
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Research Article
TTR Exon-Humanized Mice as a Model for Genotype-Dependent Transthyretin Deposition: Supportive Evidence for RBP4 as a Natural Stabilizer
Author(s): Zhenghua Li, Hideki Kanazashi, Yuya Murakami, Rie Fujikawa, Naoko Matsushita, Toru Takeo, Aki Sugano, Mika Ohta, Yutaka Takaoka and Kenichi Yamamura*
Transthyretin amyloidosis is caused by destabilization, dissociation, and tissue deposition of transthyretin (TTR). Although several transgenic and knock-in mouse models have been generated, many models are limited by non- physiological copy number, low expression, or the formation of hybrid tetramers between mouse and human TTR. We previously generated TTR exon-humanized mice in which mouse Ttr exons were replaced with corresponding human TTR exons while preserving the mouse genomic structure. In the present study, we introduced the Val30Met mutation into the TTR exon-humanized allele and generated three genotypes: TtrhTTRV30e/hTTRV30e, TtrhTTRM30e/hTTRM30e, and TtrhTTRV30e/hTTRM30e mice. We examined non-fibrillar human TTR deposition by immunohistochemistry in ileum, kidney, and sciatic nerve at 26 and 52 weeks of age, using a semi-quantitative scoring system. Genotype-dependent TTR.. Read More»