Impairment of learning and memory in TAG-1 deficient mice associated with shorter CNS internodes and disrupted juxtaparanodes

Mol Cell Neurosci. 2008 Nov;39(3):478-90. doi: 10.1016/j.mcn.2008.07.025. Epub 2008 Aug 9.


The cell adhesion molecule TAG-1 is expressed by neurons and glial cells and plays a role in axon outgrowth, migration and fasciculation during development. TAG-1 is also required for the clustering of Kv1.1/1.2 potassium channels and Caspr2 at the juxtaparanodes of myelinated fibers. Behavioral examination of TAG-1 deficient mice (Tag-1(-/-)) showed cognitive impairments in the Morris water maze and novel object recognition tests, reduced spontaneous motor activity, abnormal gait coordination and increased response latency to noxious stimulation. Investigation at the molecular level revealed impaired juxtaparanodal clustering of Caspr2 and Kv1.1/1.2 in the hippocampus, entorhinal cortex, cerebellum and olfactory bulb, with diffusion into the internode. Caspr2 and Kv1.1 levels were reduced in the cerebellum and olfactory bulb. Moreover, Tag-1(-/-) mice had shorter internodes in the cerebral and cerebellar white matter. The detected molecular alterations may account for the behavioural deficits and hyperexcitability in these animals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / ultrastructure*
  • Behavior, Animal / physiology
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Central Nervous System / anatomy & histology*
  • Central Nervous System / metabolism
  • Contactin 2
  • Humans
  • Kv1.1 Potassium Channel / genetics
  • Kv1.1 Potassium Channel / metabolism
  • Kv1.2 Potassium Channel / genetics
  • Kv1.2 Potassium Channel / metabolism
  • Learning Disabilities / physiopathology*
  • Male
  • Memory Disorders / physiopathology*
  • Mice
  • Mice, Knockout
  • Myelin Sheath / metabolism
  • Neuropsychological Tests


  • CNTN2 protein, human
  • Cell Adhesion Molecules, Neuronal
  • Cntn2 protein, mouse
  • Contactin 2
  • Kv1.2 Potassium Channel
  • Kv1.1 Potassium Channel