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Loss of CNTNAP2 causes axonal excitability deficits, developmental delay in cortical myelination, and abnormal stereotyped motor behavior

Scott, R., Sánchez-Aguilera, A., van Elst, K., Lim, L., Dehorter, N., Bae, S. E., Bartolini, G., Peles, E., Kas, M. J. H., Bruining, H. & Marín, O., 1-Feb-2019, In : Cerebral Cortex. 29, 2, p. 586–597 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Ricardo Scott
  • Alberto Sánchez-Aguilera
  • Kim van Elst
  • Lynette Lim
  • Nathalie Dehorter
  • Sung Eun Bae
  • Giorgia Bartolini
  • Elior Peles
  • Martien J H Kas
  • Hilgo Bruining
  • Oscar Marín

Contactin-associated protein-like 2 (Caspr2) is found at the nodes of Ranvier and has been associated with physiological properties of white matter conductivity. Genetic variation in CNTNAP2, the gene encoding Caspr2, has been linked to several neurodevelopmental conditions, yet pathophysiological effects of CNTNAP2 mutations on axonal physiology and brain myelination are unknown. Here, we have investigated mouse mutants for Cntnap2 and found profound deficiencies in the clustering of Kv1-family potassium channels in the juxtaparanodes of brain myelinated axons. These deficits are associated with a change in the waveform of axonal action potentials and increases in postsynaptic excitatory responses. We also observed that the normal process of myelination is delayed in Cntnap2 mutant mice. This later phenotype is a likely modulator of the developmental expressivity of the stereotyped motor behaviors that characterize Cntnap2 mutant mice. Altogether, our results reveal a mechanism linked to white matter conductivity through which mutation of CNTNAP2 may affect neurodevelopmental outcomes.

Original languageEnglish
Pages (from-to)586–597
Number of pages12
JournalCerebral Cortex
Volume29
Issue number2
Early online date28-Dec-2017
Publication statusPublished - 1-Feb-2019

    Keywords

  • Journal Article

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