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論文
- タイトル
- タイトル（英）
- Identification of novel amyloidosis in dogs: α-S1-casein acquires amyloidogenicity in mammary tumor by overexpression and N-terminal truncation.
- 参照URL
- https://researchmap.jp/alz42/published_papers/41317520
- 著者
- 著者（英）
- Tomoaki Murakami,Toshisuke Kaku,Kaori Tsukakoshi,Susumu Iwaide,Yoshiyuki Itoh,Miki Hisada,Kohji Nomura,Rikako Kubo,Kazunori Ikebukuro,Yukiko Sassa-O'Brien,Fuyuki Kametani
- 担当区分
- 概要
- 概要（英）
- Mammary tumor-associated amyloidosis (MTAA) in dogs is characterized by amyloid deposition in the stroma of mammary adenoma or carcinoma; however, the amyloid precursor protein remains unknown. We attempted to identify an amyloid precursor protein and elucidated its etiology by characterizing 5 cases of canine MTAA. Proteomic analyses of amyloid extracts from formalin-fixed paraffin-embedded specimens revealed α-S1-casein (CASA1) as a prime candidate and showed the N-terminal truncation of canine CASA1. Both immunohistochemistry and immunoelectron microscopy showed that amyloid deposits or fibrils in MTAA cases were positive for CASA1. Reverse transcription-polymerase chain reaction and quantitative polymerase chain reaction revealed the complete mRNA sequence encoding CASA1, whose expression was significantly higher in the amyloid-positive group. The recombinant protein of the N-terminal-truncated canine CASA1 and the synthetic peptides derived from canine and human CASA1 formed amyloid-like fibrils in vitro. Structural prediction suggested that the N-terminal region of CASA1 was disordered. Previously, full-length CASA1 was reported to inhibit the amyloidogenesis of other proteins; however, we demonstrated that CASA1 acquires amyloidogenicity via excessive synthesis followed by truncation of its disordered N-terminal region. By identifying a novel in vivo amyloidogenic protein in animals and revealing key mechanistic details of its associated pathology, this study provides valuable insights into the integrated understanding of related proteopathies.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Veterinary pathology
- 巻
- 号
- 開始ページ
- 3009858221148511
- 終了ページ
- 3009858221148511
- 出版年月
- 2023年1月21日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1177/03009858221148511
- 共同研究・競争的資金等の研究課題
研究者
亀谷 富由樹
(カメタニ フユキ)