Allelic Diversity in the Serum Amyloid A2 Gene and Amyloid A Amyloidosis in a Breeding Colony of Zebra Finches (Taeniopygia guttata)

A high incidence of amyloid A (AA) amyloidosis was observed in the research breeding colony of zebra finches at our institution. Some birds with hepatic AA amyloidosis were asymptomatic for comorbid conditions frequently associated with the development of AA amyloidosis, whereas other birds with comorbid conditions failed to develop AA amyloidosis, suggesting a potential genetic component to the disease. Sequencing the SAA2 gene from 20 birds yielded 18 distinct sequences that coded for 5 isoforms of the protein. Most of the amino acid substitutions are unlikely to affect the protein's structure or function, but 2 changes—R52L and V84M—were predicted to be disruptive. In particular, R52 is highly conserved across vertebrates, with only arginine or lysine found at this position in reported sequences to date. The atypical R52L substitution occurred in 2 otherwise healthy birds with hepatic AA amyloidosis, supporting the idea that this change is pathogenic.

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Aggregation of Mouse Serum Amyloid A Protein Was Promoted by Amyloid-Enhancing Factors with the More Genetically Homologous Serum Amyloid A

International Journal of Molecular Sciences ◽

10.3390/ijms22031036 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1036

Author(s):

Xuguang Lin ◽

Kenichi Watanabe ◽

Masahiro Kuragano ◽

Kiyotaka Tokuraku

Keyword(s):

Amino Acid ◽

Serum Amyloid A ◽

Animal Species ◽

Amino Acid Sequences ◽

Serum Amyloid ◽

Mouse Serum ◽

Aa Amyloidosis ◽

Basic Residue ◽

Amyloid A ◽

Serum Amyloid A Protein

Amyloid A (AA) amyloidosis is a condition in which amyloid fibrils characterized by a linear morphology and a cross-β structure accumulate and are deposited extracellularly in organs, resulting in chronic inflammatory diseases and infections. The incidence of AA amyloidosis is high in humans and several animal species. Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis. Amyloid enhancing factor (AEF) serves as a seed for fibril formation and shortens the onset of AA amyloidosis sharply. In this study, we examined whether AEFs extracted and purified from five animal species (camel, cat, cattle, goat, and mouse) could promote mouse SAA (mSAA) protein aggregation in vitro using quantum-dot (QD) nanoprobes to visualize the aggregation. The results showed that AEFs shortened and promoted mSAA aggregation. In addition, mouse and cat AEFs showed higher mSAA aggregation-promoting activity than the camel, cattle, and goat AEFs. Interestingly, homology analysis of SAA in these five animal species revealed a more similar amino acid sequence homology between mouse and cat than between other animal species. Furthermore, a detailed comparison of amino acid sequences suggested that it was important to mSAA aggregation-promoting activity that the 48th amino acid was a basic residue (Lys) and the 125th amino acid was an acidic residue (Asp or Glu). These data imply that AA amyloidosis exhibits higher transmission activity among animals carrying genetically homologous SAA gene, and may provide a new understanding of the pathogenesis of amyloidosis.

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Identification of a novel serum amyloid A protein in BALB/c mice

Biochemical Journal ◽

10.1042/bj2800045 ◽

1991 ◽

Vol 280 (1) ◽

pp. 45-49 ◽

Cited By ~ 27

Author(s):

M C de Beer ◽

C M Beach ◽

S I Shedlofsky ◽

F C de Beer

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Isoelectric Focusing ◽

Serum Amyloid A ◽

Serum Amyloid ◽

The Other ◽

Amino Acid Substitutions ◽

Gene Products ◽

Amyloid A ◽

Serum Amyloid A Protein

Four serum amyloid A protein (SAA) genes and two SAA gene products, SAA1 and SAA2, were identified in BALB/c mice. Using analytical isoelectric focusing we have identified a quantitatively significant new member of the SAA family and designated it ‘SAA5’. This protein has characteristics never before described for any SAA molecule. In the highly conserved region between amino acids 33 and 44, identical in all SAAs from all species examined, SAA5 had four amino acid substitutions. In addition, the induction of SAA5 by lipopolysaccharide had different kinetics from that of the other mouse SAAs. Our data suggest that the mouse SAA gene family is more complex in composition and regulation than previously surmised.

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Recombinant Variants of Tissue-Type Plasminogen Activator Containing Amino Acid Substitutions in the Finger Domain

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646342 ◽

1992 ◽

Vol 68 (06) ◽

pp. 672-677 ◽

Cited By ~ 4

Author(s):

Hitoshi Yahara ◽

Keiji Matsumoto ◽

Hiroyuki Maruyama ◽

Tetsuya Nagaoka ◽

Yasuhiro Ikenaka ◽

...

Keyword(s):

Amino Acid ◽

Plasminogen Activator ◽

Half Life ◽

Tissue Type ◽

Clot Lysis ◽

Amino Acid Substitutions ◽

Wild Type ◽

Plasma Clot ◽

Tissue Type Plasminogen Activator ◽

Type Plasminogen Activator

SummaryTissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7–9, 10–14, 15–19, 28–33, and 37–42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37–42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37–42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37–42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37–42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA.

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