Slc20a2 is critical for maintaining a physiologic inorganic phosphate level in cerebrospinal fluid

Neurogenetics. 2016 Apr;17(2):125-30. doi: 10.1007/s10048-015-0469-6. Epub 2015 Dec 12.

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.

Keywords: Cerebrospinal fluid; Fahr’s disease; Inorganic phosphate; Primary familial brain calcification; SLC20A1; SLC20A2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcinosis / cerebrospinal fluid
  • Calcinosis / genetics
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation
  • Neurodegenerative Diseases / cerebrospinal fluid
  • Neurodegenerative Diseases / genetics
  • Phosphates / cerebrospinal fluid*
  • Sodium-Phosphate Cotransporter Proteins, Type III / genetics*
  • Sodium-Phosphate Cotransporter Proteins, Type III / metabolism

Substances

  • Phosphates
  • Slc20a2 protein, mouse
  • Sodium-Phosphate Cotransporter Proteins, Type III