*5.1. The PXE Mice*

Two lines of *Abcc6* knockout (*Abcc6*−/−) mice were generated independently [90,91]. In these *Abcc6*−/<sup>−</sup> mice, *Abcc6* exons 15 to 18 were deleted. Both mouse lines lack the ABCC6 protein and develop identical calcification phenotypes that are consistent with the human PXE condition. The mice breed normally and have a life span of about 25+ months. These animals display spontaneous mineralization in vascular, ocular, and renal tissues, as well as in testes and vibrissae in the whiskers. The earliest evidence of mineralization occurs at 5–6 weeks of age in the capsules of vibrissae. The calcification in vibrissae is progressive and quantifiable and thus serves as a reliable marker of disease progression [92]. Heterozygous *Abcc6*+/<sup>−</sup> mice do not develop any calcification. Similar to their human counterpart, *Abcc6*−/<sup>−</sup> mice have lowered plasma PPi [9,18] altered lipoproteins [93,94], develop Randall's plaques, and have low urinary PPi excretion [45,46]. These animals have been invaluable for understanding the pathobiology of PXE and to test crucial pathophysiological hypotheses [95,96] that in vitro approaches could partially address [97]. These mice were the ultimate tool that allowed the development of therapeutic solutions for PXE patients [18,19,92,98,99].
