title: Proteomic analysis of highly prevalent amyloid A amyloidosis endemic to endangered island foxes.
abstract: Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34%) in a genetically isolated population of island foxes (Urocyon littoralis) with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%), spleen (58%), oral cavity (45%), and vasculature (44%) and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤ 0.05). Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid deposition, a unique SAA sequence, and the co-occurrence of AA with apolipoproteins.
authors.affiliation: Departments of Pathology and Medicine, University of California San Diego, La Jolla, California, United States of America; Department of Pathology, Immunology, and Microbiology, University of California Davis, Davis, California, United States of America.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Gaffney
authors.affiliation: Department of Pathology, Immunology, and Microbiology, University of California Davis, Davis, California, United States of America.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Imai
authors.affiliation: Wildlife Investigations Laboratory, California Department of Fish and Wildlife, Rancho Cordova, California, United States of America; Department of Veterinary Medicine and Epidemiology, University of California Davis, Davis, California, United States of America.
authors.forename: Deana L
authors.initials: DL
authors.lastname: Clifford
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Majid
authors.initials: M
authors.lastname: Ghassemian
authors.affiliation: Center for Computational Biology, Institute for Genomic Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Roman
authors.initials: R
authors.lastname: Sasik
authors.affiliation: Center for Computational Biology, Institute for Genomic Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Chang
authors.affiliation: Veterinary Population Medicine Department, Veterinary Diagnostic Laboratory, University of Minnesota, St. Paul, Minnesota, United States of America.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: O'Brien
authors.affiliation: Departments of Pathology and Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Judith
authors.initials: J
authors.lastname: Coppinger
authors.affiliation: Departments of Pathology and Neuroscience, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Margarita
authors.initials: M
authors.lastname: Trejo
authors.affiliation: Departments of Pathology and Neuroscience, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Department of Pathology, Immunology, and Microbiology, University of California Davis, Davis, California, United States of America.
authors.forename: Linda
authors.initials: L
authors.lastname: Munson
authors.affiliation: Departments of Pathology and Medicine, University of California San Diego, La Jolla, California, United States of America; Department of Pathology, Immunology, and Microbiology, University of California Davis, Davis, California, United States of America.
authors.forename: Christina
authors.initials: C
authors.lastname: Sigurdson
mesh_terms: D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology / Q000662:veterinary*; D000818:Animals; D001808:Blood Vessels / Q000737:chemistry* / Q000473:pathology; D002140:California / Q000453:epidemiology; D056727:Endangered Species; D005260:Female; D005589:Foxes; D062312:Islands; D007668:Kidney / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009055:Mouth / Q000737:chemistry / Q000473:pathology; D015995:Prevalence; D040901:Proteomics; D060047:Reproductive Isolation; D000685:Serum Amyloid A Protein / Q000032:analysis* / Q000648:ultrastructure; D013154:Spleen / Q000737:chemistry / Q000473:pathology
chemical_list: D000685:Serum Amyloid A Protein