Ablation of TNAP function compromises myelination and synaptogenesis in the mouse brain.
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.
Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary.
János
J
Hanics
János
J
Barna
Jinsong
J
Xiao
José Luis
JL
Millán
Caroline
C
Fonta
László
L
Négyessy
D000469:Alkaline Phosphatase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development* / Q000378:metabolism; D055786:Gene Knockout Techniques; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development* / Q000378:metabolism; D013569:Synapses / Q000201:enzymology* / Q000378:metabolism
C510878:ALPL protein, mouse; D000469:Alkaline Phosphatase