FRM - Sarah Beck-Cormier (2024-2027)

Primary Familial Brain Calcification (PFBC) is a neurodegenerative disease characterized by calcium-phosphate (Ca-Pi) deposits mostly and primarily in mural cells of capillaries and arterioles (pericytes and vascular smooth muscle cells), and associated with neuropsychiatric and motor disorders, with high impact on life quality, but no specific treatment is currently available.

So far, seven genes have been associated to PFBC and account for only 50% of patients. Among these genes, two encode Pi transporters (SLC20A2 and XPR1), and two others controls the expression of Slc20a2 at the plasma membrane. However, the molecular mechanisms underlying the dysfunctional role of PFBC genes in the induction of calcification and the appearance of clinical symptoms remains unknown.

Our objective is to better understand the cellular and molecular mechanisms underlying the pathophysiology of PFBC disease. We also particularly focus on the roles of mural cells in brain vessel calcifications.

To reach this objective, we use and develop several mouse models:

• The Slc20a2-/- model (Beck-Cormier et al JBMR 2019)
• Thanks to the Foundation Maladie Rare we have generated a novel mouse model carrying the most frequently found mutation in XPR1 gene in patients :
• Conditional KO of Slc20a2 and Xpr1 in mural cells