Inhibition of Tissue-Nonspecific Alkaline Phosphatase Attenuates Ectopic Mineralization in the Abcc6

Qiaoli Li
Jianhe Huang
Anthony B Pinkerton
Jose Luis Millan
B D van Zelst
Michael A Levine
John P Sundberg, The Jackson Laboratory
Jouni Uitto


Pseudoxanthoma elasticum (PXE), a prototype of heritable ectopic mineralization disorders, is caused by mutations in the ABCC6 gene encoding a putative efflux transporter ABCC6. It was recently demonstrated that the absence of ABCC6-mediated ATP release from the liver, and consequently reduced PPi levels, underlie the pathogenesis of PXE. Given that tissue-nonspecific alkaline phosphatase (TNAP), encoded by ALPL, is the enzyme responsible for degrading PPi, we hypothesized that reducing TNAP levels either by genetic or pharmacological means would lead to amelioration of the ectopic mineralization phenotype in the Abcc6