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A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression.

Migraine is a common, disabling, multifactorial, episodic neurovascular disorder of unknown etiology. Familial hemiplegic migraine type 1 (FHM-1) is a Mendelian subtype of migraine with aura that is caused by missense mutations in the CACNA1A gene that encodes the alpha(1) subunit of neuronal Ca(v)2.1 Ca(2+) channels. We generated a knockin mouse model carrying the human pure FHM-1 R192Q mutation and found multiple gain-of-function effects. These include increased Ca(v)2.1 current density in cerebellar neurons, enhanced neurotransmission at the neuromuscular junction, and, in the intact animal, a reduced threshold and increased velocity of cortical spreading depression (CSD; the likely mechanism for the migraine aura). Our data show that the increased susceptibility for CSD and aura in migraine may be due to cortical hyperexcitability. The R192Q FHM-1 mouse is a promising animal model to study migraine mechanisms and treatments.

Pubmed ID: 15003170


  • van den Maagdenberg AM
  • Pietrobon D
  • Pizzorusso T
  • Kaja S
  • Broos LA
  • Cesetti T
  • van de Ven RC
  • Tottene A
  • van der Kaa J
  • Plomp JJ
  • Frants RR
  • Ferrari MD



Publication Data

March 4, 2004

Associated Grants

  • Agency: Telethon, Id: E.0847
  • Agency: Telethon, Id: E.1297

Mesh Terms

  • Animals
  • Calcium Channels
  • Calcium Channels, N-Type
  • Calcium Channels, P-Type
  • Calcium Channels, Q-Type
  • Cells, Cultured
  • Cortical Spreading Depression
  • Disease Models, Animal
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Migraine with Aura
  • Motor Endplate
  • Mutation
  • Recombination, Genetic