Ablation of TNAP function compromises myelination and synaptogenesis in the mouse brain

János Hanics, János Barna, Jinsong Xiao, José Luis Millán, Caroline Fonta, László Négyessy

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25 Citations (Scopus)

Abstract

Mutations in the tissue-nonspecific alkaline phosphatase (TNAP) gene can result in skeletal and dental hypomineralization and severe neurological symptoms. TNAP is expressed in the synaptic cleft and the node of Ranvier in normal adults. Using TNAP knockout (KO) mice (Akp2-/-), we studied synaptogenesis and myelination with light- and electron microscopy during the early postnatal days. Ablation of TNAP function resulted in a significant decrease of the white matter of the spinal cord accompanied by ultrastructural evidence of cellular degradation around the paranodal regions and a decreased ratio and diameter of the myelinated axons. In the cerebral cortex, myelinated axons, while present in wild-type, were absent in the Akp2-/- mice and these animals also displayed a significantly increased proportion of immature cortical synapses. The results suggest that TNAP deficiency could contribute to neurological symptoms related to myelin abnormalities and synaptic dysfunction, among which epilepsy, consistently present in the Akp2-/- mice and observed in severe cases of hypophosphatasia.

Original languageEnglish
Pages (from-to)459-471
Number of pages13
JournalCell And Tissue Research
Volume349
Issue number2
DOIs
Publication statusPublished - Jun 14 2012

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Keywords

  • Alkaline phosphatase
  • Electron microscopy
  • Epilepsy
  • Hypophosphatasia
  • Node of Ranvier

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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