Identification of novel amyloidosis in dogs: α-S1-casein acquires amyloidogenicity in mammary tumor by overexpression and N-terminal truncation

Murakami, Tomoaki; Kaku, Toshisuke; Tsukakoshi, Kaori; Iwaide, Susumu; Itoh, Yoshiyuki; Hisada, Miki; Nomura, Kohji; Kubo, Rikako; Sassa-O’Brien, Yukiko; Kametani, Fuyuki

doi:10.1177/03009858221148511

Cited by 9 publications

(11 citation statements)

References 56 publications

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“…FFPE specimens of all cases were cut into 8 µm sections, put on PEN membrane glass slides (Thermo Fisher Scientific, Tokyo, Japan), and stained with Congo red. Dissection, solubilization and tryptic digestion of Congo-red-positive amyloid lesions were performed, as described previously [ 8 ]. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) of digested and MS/MS data acquisition were performed as described previously [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

“…Dissection, solubilization and tryptic digestion of Congo-red-positive amyloid lesions were performed, as described previously [ 8 ]. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) of digested and MS/MS data acquisition were performed as described previously [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

“…Cerebral amyloidosis, observed in Alzheimer’s disease, is another type of localized amyloidosis in humans [ 3 , 4 ]. In animals, localized amyloidosis has been linked to neoplastic conditions, such as pancreatic endocrine tumor [ 5 ], medullary thyroid carcinoma [ 6 ], ameloblastoma [ 7 ], mammary carcinoma [ 8 ], intestinal carcinoid [ 9 ], extramedullary plasmacytoma [ 10 , 11 ], and myeloma [ 12 ]. Localized amyloid deposition in odontogenic tumors has been reported in cats, dogs, a goat, a prairie dog ( Cynomys ludovicianus ), and a Bengal tiger ( Panthera tigris tigris ) [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification of Ameloblastin as an Amyloid Precursor Protein of Amyloid-Producing Ameloblastoma in Dogs and Cats

Masoud

Iwaide

Itoh

et al. 2023

Veterinary Sciences

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Amyloid-producing ameloblastoma (APAB) is characterized by abundant amyloid deposits in ameloblastoma, but the amyloid precursor protein is unknown. To explore this, we conducted histopathologic and proteomic analyses on formalin-fixed and paraffin-embedded samples from five cases of APAB (three dogs and two cats). Histologically, the samples exhibited a proliferation of the odontogenic epithelium, with moderate to severe interstitial amyloid deposits. By using Congo red and polarized light, the amyloid deposits were found to show characteristic birefringence. Amyloid deposits were dissected from tissue sections and analyzed by LC/MS/MS, and high levels of ameloblastin were detected in all tissues. Mass spectrometry also revealed that the N-terminal region of ameloblastin is predominantly present in amyloid deposits. Immunohistochemistry was performed using two anti-ameloblastin (N terminal, middle region) antibodies and showed that amyloid deposits were positive for ameloblastin N terminal but negative for ameloblastin middle region. These results suggest that ameloblastin is the amyloid precursor protein of APABs in dogs and cats, and the N-terminal region may be involved in the amyloidogenesis of ameloblastin.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of Ameloblastin as an Amyloid Precursor Protein of Amyloid-Producing Ameloblastoma in Dogs and Cats

Masoud

Iwaide

Itoh

et al. 2023

Veterinary Sciences

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“…Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of amyloid deposits collected from Congo red-stained sections was performed to determine the protein pro le in the amyloid deposits. As in the previous study 11,12 , Congo red-positive amyloid deposits in glomeruli, outer medulla, and papillae were collected from ve regions of approximately 500,000 µm 2 each under a stereomicroscope. Three samples of each collection were digested with trypsin, and two samples were digested with chymotrypsin before LC-MS/MS analysis, as described previously 11,12 .…”

Section: Tissue Microdissection and Mass Spectrometrymentioning

confidence: 99%

Divergent renal localization patterns of heterozygote-derived two distinct AA amyloids in a cat

Kobayashi,

Kaneda,

Iwaide

et al. 2024

Preprint

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Amyloid A (AA) amyloidosis poses a fatal threat to both humans and animals. While the kidneys represent the principal organ affected in AA amyloidosis, there exists variability in the localization of amyloid deposition, with distinct symptoms delineated by the specific deposition sites. Nevertheless, the factors contributing to the diversity of deposition remain unclear. In this study, we identified an association between serum amyloid A (SAA) polymorphisms and patterns of amyloid deposition. Histopathological analysis of the kidneys from a 5-year-old spayed female Japanese cat, which succumbed to systemic AA amyloidosis, revealed renal amyloid deposition in cortical glomeruli and medullary interstitium. Genetic analysis disclosed that the afflicted cat possessed a heterozygous SAA with three amino acid substitutions (K47I, Q63R, S93N), resulting in the SAAKQS and SAAIRN variants. Mass spectrometry and immunohistochemistry demonstrated that SAAKQS was deposited in the glomerulus and renal papilla, while SAAIRN was restricted to the extramedullary zone. This study established the differing renal distributions of two AA amyloid variants originating from heterozygotes within a single individual. The evidence supports the notion that the primary structure of precursor proteins defines the distribution of amyloid deposition.

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“…Tissue microdissection, sample processing, tryptic digestion, dithiothreitol reduction, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) of the digested peptides were performed as described previously. 13 The resulting MS/MS data were collated with the theoretical fragmentation patterns of tryptic peptide sequences of porcine proteins registered in the UniProt database using the Mascot Server (Matrix Science Inc., Boston, MA, USA). “semiTrypsin” was used as the in silico proteolytic enzyme.…”

Section: Tissue Microdissection and Proteomic Analysismentioning

confidence: 99%

Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs

Inoue,

Miyazaki,

Kobayashi

et al. 2023

Toxicol Pathol

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The minipig has been used as a non-rodent species in nonclinical toxicology studies, but little is known about amyloid A (AA) amyloidosis in this species. Among domestic pigs, reports of AA amyloidosis have been limited to animals with mutations in the N-terminal residue of serum AA (SAA), which is thought to be a primary etiological factor. In this study, we histologically examined 26 microminipigs aged 0.6 to 10 years and observed amyloid deposition in one 0.6-year-old and six 5-year-old or older microminipigs. The amyloid deposits were identified as AA based on mass spectrometry (MS) and immunohistochemistry (IHC). The 0.6-year-old microminipig showed severe deposition in the renal cortex and spleen, whereas 5-year-old or older animals had severe deposition in the renal medulla. MS and IHC detected serum amyloid P-component (SAP) in amyloid deposits in older animals but not in a 0.6-year-old animals. Based on the proteomic analysis and gene sequencing, amino acid mutations of SAA, previously found in domestic pigs, were not involved in the pathogenesis of AA amyloidosis in microminipigs. This study demonstrates that microminipigs with wild-type SAA develop AA amyloidosis and presents the possibility that differences in the environment surrounding amyloid, such as SAP, may influence differences in the pathological phenotype.

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Identification of novel amyloidosis in dogs: α-S1-casein acquires amyloidogenicity in mammary tumor by overexpression and N-terminal truncation

Cited by 9 publications

References 56 publications

Identification of Ameloblastin as an Amyloid Precursor Protein of Amyloid-Producing Ameloblastoma in Dogs and Cats

Identification of Ameloblastin as an Amyloid Precursor Protein of Amyloid-Producing Ameloblastoma in Dogs and Cats

Divergent renal localization patterns of heterozygote-derived two distinct AA amyloids in a cat

Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs

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