The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders

Table 2

Mineralization phenotypes of PXE-related murine strains (based on [60]).

Strain	Phenotype
129S1/SvImJ	Fibroosseous bone lesions; Vibrissae mineralization
C3H/HeJ	Epicardial fibrosis and mineralization; Fibroosseous bone lesions
DBA/2J	Epicardial fibrosis and mineralization; Fibroosseous bone lesions; Arterial mineralization
KK/HIJ	Systemic mineralization (lung, retina); Epicardial fibrosis and mineralization; Fibroosseous bone lesions; Arterial mineralization; Vibrissae mineralization; Hyperplasia (most common in pancreatic islets) 24009271
Abcc6^−/− (targeted ablation)	Spontaneous calcification of EFs (mainly in arteries, the renal cortex, and the capsule surrounding the sinuses of the vibrissae); Normal plasma mineral levels; Mineralization of dermal EFs and collagen; Lower plasma HDL cholesterol; Increased plasma creatinine
Abcc6^−/− (deletion of NBF1)	Spontaneous calcification of EFs (mainly in arteries, the renal cortex, and the capsule surrounding the sinuses of the vibrissae); Normal plasma mineral levels
DCC or Dyscalc	Myocardial calcification; Absence of vascular and vibrissa calcification

This lesion was also found in strains without PXE-like mineralization and was not linked to EF calcification. Probably this lesion is thus not associated with PXE or Abcc6 was a strong modifier gene in KK/HIJ mice when mutated [60]. The other described lesions, apart from hyperplasia in the KK/HIJ mouse, can be linked to PXE. NBF1: nucleotide-binding fold 1.