Amyloidosis is a rare disease caused by extracellular deposition of insoluble abnormal fibrils derived from aggregation of a misfolded variant of a normally soluble protein. Apolipoprotein (apo) AII is a major protein of HDL (high density lipoproteins) synthesized in liver. An apo AII variant carrying a mutation in the Stop codon causes an autosomal dominant apoa2-amyloidosis in humans (Yazaki et al, Kidney Int 2001, 60:1658-65). As in humans, our transgenic mice for the mutant human apo a2 gene with a Stop codon to Serine mutation (Stop78->Ser) express a longer hapo AII protein (99 AA instead of 77).Characteristics of transgenic mice:
• Spontaneous systemic amyloidosis begins as early as 3-4 months of age and increases as a function of age, with no need for an inflammatory state. Mouse lifespan varies between 6 and 9 months, depending on the gravity of amyloidosis.
• Amyloid fibrils stain with Congo red with the characteristic green birefringence under polarized light.
• Amyloid fibrils have been characterized by immunohistochemistry with human-apoAII antibodies in kidney, liver, heart spleen, and by electron microscopy in capillaries of liver and heart.
• Amyloid fibrils have been isolated from tissues; solubilized amyloid fibril protein was fractionated and the amino acid sequence of full-length hapoAII with a 21 amino acid carboxyl terminal extension was verified.