We have been investigating an unusual protein found in serum of Syrian hamsters that is preferentially expressed in Female hamster. This protein, called Female protein (FP) is a major serum protein in females (2-3 mg/ml serum) but concentration in normal male serum is 100-300 fold less. This protein is synthesized in the liver and has an unusual structure being made of 5 identical monomeric subunits non covalently assembled as a cyclic pentamer. It is homologous with two human proteins, C-Reactive protein (CRP) and serum amyloid P component (SAP), sharing a 50-70% (respectively) of their identical amino acid sequence. This family of proteins is call pentraxin, and these proteins are widely expressed in nature, and show little change during evolution. Their antiquity is illustrated by the presence of a distinct homolog in the horseshoe crab. The conservative evolution and antiquity suggests a biologically important function for pentraxin although a critical role has not been formed. FP shares many properties with CRP and SAP including phosphorocholine and galactan binding, complement fixation and acute phase responsiveness. The unusual hormonal control of FP suggests that this pentraxin may have a unequal sex-limited function in the hamster, that could provide information about the general function of all pentraxins. FP is also a constituent of amyloid. Amyloid deposits in humans are most commonly found in brain of patients with Alzheimer's disease. Amyloidosis is a common disease in Syrian hamster, especially in females where virtually 100% are affected by 1 yr. of age. When serum FP levels were hormonally manipulated, we showed that amyloidosis in male & female Syrian hamster was directly related to FP concentration in serum. A very similar FP was formed in the Turkish hamster (Mesocricetus brandti) a close relation of the Syrian hamster (Mesocricetus auratus). However, amyloidosis is rare in Turkish hamsters, who also have much lower levels of FP in serum. Another unusual feature of the Pentraxin family of proteins is the heretofore unreported existence of polymorphic pentraxins. However, we have found a FP polymorphism that is detectable by protein electrophoresis. This so called electrophoretically slow FP was found in 3 inbred strains of Syrian hamster that were derived from a new (1971) capture of wild hamsters in Syria. This slow FP is indistinguishable form regular (fast) FP by biological and functional analysis. The polymorphism does represent a structural difference in the protein backbone of the molecule, because the uniquely different mobility (charge) is still detectable after removal of the carbohydrate. Progeny from fast and slow FP parents demonstrated an FP of intermediate mobility, that was shown to be the result of hybrid pentamers constructed from fast and slow monomers. Such hybrid pentamers could not be formed in vitro and presumably represent co expression and assemblage of both fast and slow FP variants within a single hepatocyte. The finding of this unique pentraxin polymorphism in hamster again illustrates the unusual expression of pentraxins in this species.
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