Abstract
Mutations in the SLC20A2-gene encoding the inorganic phosphate (Pi) transporter PiT2 can explain approximately 40 % of the familial cases of the rare neurodegenerative disorder primary familial brain calcification (Fahr’s disease). The disease characteristic, cerebrovascular-associated calcifications, is also present in Slc20a2-knockout (KO) mice. Little is known about the specific role(s) of PiT2 in the brain. Recent in vitro studies, however, suggest a role in regulation of the [Pi] in cerebrospinal fluid (CSF). We here show that Slc20a2-KO mice indeed have a high CSF [Pi] in agreement with a role of PiT2 in Pi export from the CSF. The implications in relation to disease mechanism are discussed.
Highlights
Primary familial brain calcification (PFBC), formerly Fahr’s disease, is a rare autosomal dominantly inherited neurodegenerative disorder with neuropsychiatric and motor symptoms
The localizations were confirmed on sections of rat lateral choroid plexus (ChP) [34]. These results suggest that PiT2 plays a major role in maintaining the low [Pi] in the cerebrospinal fluid (CSF) by exporting Pi from the CSF to the blood
To address whether Slc20a2-KO mice have an elevated [Pi] in the CSF, we measured the [Pi] in CSF and blood drawn from 3-week-old Slc20a2-KO mice and WT litter mates
Summary
Primary familial brain calcification (PFBC), formerly Fahr’s disease, is a rare autosomal dominantly inherited neurodegenerative disorder with neuropsychiatric and motor symptoms. It is characterized by calcifications in the basal ganglia and other brain regions. In vitro studies show that exposure of vascular smooth muscle cells to hyperphosphatemic conditions leads to trans-differentiation to a mineralizing cell-type [22]. Based on studies of vascular smooth muscle cells, a key step in the Pi-induced calcification process is deregulated expression of type III NaPi symporters, which besides SLC20A2 comprise the highly related SLC20A1 [24]. Individuals with PFBC do, not show elevated serum [Pi] [1, 5, 25], and the function and role of PiT2 in relation to PFBC are not known
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
