Characterization of the Cheetah Serum Amyloid A1 Gene: Critical Role and Functional Polymorphism of a Cis-Acting Element

Zhang, Beiru; Une, Yumi; F, Ge; Fu, Xiaoying; Qian, Jin; Zhang, Pengyao; Sawashita, Jinko; Higuchi, Kenichi; Mori, Masayuki

doi:10.1093/jhered/esn015

Cited by 16 publications

(20 citation statements)

References 37 publications

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“…Given that the high incidence of AA amyloidosis in cheetahs may be due to unique features of the SAA gene in this species, we cloned and characterized the cheetah SAA1 gene. 6,81 Genome walking and polymerase chain reaction (PCR) cloning analysis revealed that cheetahs have 4 SAA genes on the same chromosome: SAA1A, SAA1B, SAA3A, and SAA3B. Of these, SAA1A and SAA1B genes show a high degree of nucleotide sequence identity, and the SAA1A and SAA1B proteins have the same amino acid sequences.…”

Section: 35mentioning

confidence: 99%

Transmission of Systemic AA Amyloidosis in Animals

2013

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Amyloidoses are a group of protein-misfolding disorders that are characterized by the deposition of amyloid fibrils in organs and/ or tissues. In reactive amyloid A (AA) amyloidosis, serum AA (SAA) protein forms deposits in mice, domestic and wild animals, and humans that experience chronic inflammation. AA amyloid fibrils are abnormal b-sheet-rich forms of the serum precursor SAA, with conformational changes that promote fibril formation. Extracellular deposition of amyloid fibrils causes disease in affected animals. Recent findings suggest that AA amyloidosis could be transmissible. Similar to the pathogenesis of transmissible prion diseases, amyloid fibrils induce a seeding-nucleation process that may lead to development of AA amyloidosis. We review studies of possible transmission in bovine, avian, mouse, and cheetah AA amyloidosis.

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Section: 35mentioning

confidence: 99%

Transmission of Systemic AA Amyloidosis in Animals

2013

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“…A point mutation in the SAA promoter was found in highly inbred captive cheetahs that have an extraordinarily high prevalence of AA amyloidosis (70%) [24]. This point mutation increased SAA transcription under inflammatory conditions in vitro [24], [25].…”

Section: Introductionmentioning

confidence: 98%

Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes

et al. 2014

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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.

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“…29 Similarly, in captive cheetahs, a SNP in the SAA promoter increases SAA transcription under pro-inflammatory conditions in vitro. 59 …”

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confidence: 99%

Systemic Amyloid A Amyloidosis in Island Foxes (Urocyon littoralis)

et al. 2015

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Systemic amyloid A (AA) amyloidosis is highly prevalent (34%) in endangered island foxes (Urocyon littoralis) and poses a risk to species recovery. Although elevated serum amyloid A from prolonged or recurrent inflammation predisposes to AA amyloidosis, additional risk factors are poorly understood. Here we define the severity of glomerular and medullary renal amyloid and identify risk factors for AA amyloidosis in 321 island foxes necropsied from 1987 through 2010. In affected kidneys, amyloid more commonly accumulated in the medullary interstitium than in the glomeruli [98% (78/80) versus 56% (45/80), respectively, p < 0.0001], and medullary deposition was more commonly severe [19% (20/105)] as compared to glomeruli [7% (7/105), p = 0.01]. Univariate odds ratios (ORs) of severe renal AA amyloidosis were greater for short- and long-term captive foxes compared to free-ranging (OR=3.2, 3.7, respectively, overall p = 0.05) and females compared to males (OR = 2.9, p = 0.05). Multivariable logistic regression revealed independent risk factors for amyloid development were increasing age class (OR = 3.8, p < 0.0001), San Clemente Island subspecies compared to San Nicolas Island subspecies (OR = 5.3, p = 0.0003), captivity (OR = 5.1, p = 0.0001), and nephritis (OR = 2.3, p = 0.01). The increased risk associated with the San Clemente subspecies or captivity suggests roles for genetic as well as exogenous risk factors in the development of AA amyloidosis.

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Characterization of the Cheetah Serum Amyloid A1 Gene: Critical Role and Functional Polymorphism of a Cis-Acting Element

Cited by 16 publications

References 37 publications

Transmission of Systemic AA Amyloidosis in Animals

Transmission of Systemic AA Amyloidosis in Animals

Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes

Systemic Amyloid A Amyloidosis in Island Foxes (Urocyon littoralis)

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