Identification of novel amyloidosis in dogs: α-S1-casein acquires amyloidogenicity in mammary tumor by overexpression and N-terminal truncation
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- Tomoaki Murakami
- Tokyo University of Agriculture and Technology, Fuchu-shi, Japan
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- Toshisuke Kaku
- Tokyo University of Agriculture and Technology, Koganei-shi, Japan
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- Kaori Tsukakoshi
- Tokyo University of Agriculture and Technology, Koganei-shi, Japan
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- Susumu Iwaide
- Tokyo University of Agriculture and Technology, Fuchu-shi, Japan
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- Yoshiyuki Itoh
- Tokyo University of Agriculture and Technology, Fuchu-shi, Japan
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- Miki Hisada
- Tokyo University of Agriculture and Technology, Fuchu-shi, Japan
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- Kohji Nomura
- Marupi Lifetech Co. Ltd., Ikeda-shi, Japan
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- Rikako Kubo
- Tokyo University of Agriculture and Technology, Koganei-shi, Japan
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- Kazunori Ikebukuro
- Tokyo University of Agriculture and Technology, Koganei-shi, Japan
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- Yukiko Sassa-O’Brien
- Tokyo University of Agriculture and Technology, Fuchu-shi, Japan
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- Fuyuki Kametani
- Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
抄録
<jats:p> 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. </jats:p>
収録刊行物
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- Veterinary Pathology
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Veterinary Pathology 60 (2), 203-213, 2023-01-21
SAGE Publications
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キーワード
詳細情報 詳細情報について
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- CRID
- 1360580232143720576
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- ISSN
- 15442217
- 03009858
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- データソース種別
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- Crossref
- KAKEN