Pseudoxanthoma elasticum (PXE), a pleiotropic heritable disorder, is characterized
by ectopic mineralization of the connective tissues. This disease is caused by mutations
in the ABCC6 gene, which is expressed primarily in the baso-lateral surface of hepatocytes,
and Abcc6(-/-) mice develop progressive mineralization mimicking human PXE. To investigate
the hypothesis that PXE is a metabolic disorder, potentially caused by the absence
of antimineralization factor(s) in circulation, we used parabiotic pairing, ie, surgical
joining of two mice, to create a shared circulation between various Abcc6 genotypic
mice. To prevent immune reaction between the parabiotic animals, all mice were bred
to be Rag1(-/-). Shared circulation between the parabiotic animals was confirmed by
Evans blue dye injection and by quantitative PCR of blood cell genotypes. Pairing
of Abcc6(-/-) mice with their wild-type counterparts halted the connective tissue
mineralization in the knockout mice. Homogenetic wild-type and heterozygous pairings
serving as controls were phenotypically unaffected by parabiosis. Consequently, the
observations on the parabiotic mice support the notion that PXE is a metabolic disease,
potentially due to absence of systemic antimineralization factor(s). These observations
suggest that reintroduction of the critical antimineralization factors into circulation
could provide a potential treatment for this, currently intractable, disease.