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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 \u03b1-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\u2013truncated 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>","DOI":"10.1177\/03009858221148511","type":"journal-article","created":{"date-parts":[[2023,1,21]],"date-time":"2023-01-21T04:52:12Z","timestamp":1674276732000},"page":"203-213","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Identification of novel amyloidosis in dogs: \u03b1-S1-casein acquires amyloidogenicity in mammary tumor by overexpression and N-terminal truncation"],"prefix":"10.1177","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-7842","authenticated-orcid":false,"given":"Tomoaki","family":"Murakami","sequence":"first","affiliation":[{"name":"Tokyo University of Agriculture and Technology, Fuchu-shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshisuke","family":"Kaku","sequence":"additional","affiliation":[{"name":"Tokyo University of Agriculture and Technology, Koganei-shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Tsukakoshi","sequence":"additional","affiliation":[{"name":"Tokyo University of Agriculture and Technology, Koganei-shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Iwaide","sequence":"additional","affiliation":[{"name":"Tokyo University of Agriculture and Technology, Fuchu-shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Itoh","sequence":"additional","affiliation":[{"name":"Tokyo University of Agriculture and Technology, Fuchu-shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Hisada","sequence":"additional","affiliation":[{"name":"Tokyo University of Agriculture and Technology, Fuchu-shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohji","family":"Nomura","sequence":"additional","affiliation":[{"name":"Marupi Lifetech Co. 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