Maine Medical Center, Medical Education, Maine Medical Center Research Institute
PRRX1 protein, human, Homeodomain Proteins, Hypophosphatemia, Phosphorus Metabolism Disorders
Hypophosphatasia (HPP) is caused by loss of function mutations in the tissuenonspecific alkaline phosphatase (TNSALP) gene (Alpl) which results in rickets, osteomalicia and bone fragility with severe childhood forms resulting in lean body mass. TNSALP is a glycosylphosphatidylinositol (GPI)-anchored phosphatase localized at the plasma membrane which when cleaved can also be found in circulation. In vitro, inhibition of TNSALP leads to a significant decrease in lipid accumulation suggesting TNSALP, an enzyme known for its mineralizing properties, may be pro-adipogenic. TNSALP has been implicated in bone marrow mesenchymal stem cell (BMMSC) lineage determination between osteoblasts and adipocytes through direct interactions with lowdensity lipoprotein receptor-related protein 6 (LRP6), modulating WNT signaling by an unknown mechanism. Alpl-/- mice die postnatally, thus, to further delineate TNSALP’s role in bone homeostasis and adipogenesis we are utilizing a Prrx1-Cre driver mated with to an Alplflfl(CreAlpflfl) mouse line.
DeMambro, Victoria; Daruszka, Jennifer; Brooks, Daniel; Bouxsein, Mary; and Rosen, Cliff, "Prrx1-CreAlplfl/flmice, a model for further investigations into the pathophysiological changes in Hypophosphatemia" (2020). Costas T. Lambrew Research Retreat 2020. 27.