Mink serum amyloid A protein. Expression and primary structure based on cDNA sequences.

Area of Science:

• Molecular Biology
• Biochemistry
• Immunology

Background:

• Serum amyloid A (SAA) is a protein involved in inflammatory responses.
• Amyloidosis is a condition characterized by the abnormal deposition of amyloid proteins.
• Previous studies suggested a single amyloidogenic SAA isotype in mink.

Purpose of the Study:

• To analyze nucleotide sequences of two mink SAA cDNA clones (SAA1 and SAA2).
• To compare derived amino acid sequences with known apoSAA and amyloid protein A (AA).
• To identify the specific SAA isotype responsible for amyloid formation in mink.

Main Methods:

• Nucleotide sequencing of SAA1 (776 bp) and SAA2 (552 bp) cDNA clones.
• Amino acid sequence comparison between mink SAA isotypes and homologous proteins.
• Analysis of SAA mRNA distribution in mink tissues after lipopolysaccharide stimulation.

Main Results:

• SAA2 cDNA clone defines the amyloid-prone isotype, while SAA1 is serum-specific.
• Six specific amino acid substitutions in SAA2 distinguish it from SAA1 and correlate with AA protein characteristics.
• Mink SAA mRNA is abundant in the liver post-stimulation, with minor presence in brain and lung; SAA mRNA is absent in amyloid-prone organs like spleen and intestine.
• A third mRNA species (2.2 kb) and two translation products (14.4 kDa and 28 kDa) were identified.

Conclusions:

• Mink SAA2 is the "amyloid prone" isotype, distinct from the serum-specific SAA1.
• The six amino acid differences in SAA2 likely contribute to its amyloidogenicity, though the exact mechanism is unknown.
• Amyloid deposition in mink is unlikely to result from locally synthesized SAA in the spleen or intestine.