Atp1a3 (ATPase, Na+/K+ transporting, alpha 3 polypeptide also known as Matoub or Matb) encodes the alpha 3 catalytic subunit of the sodium/potassium transporting ATPase transmembrane ion pump. Mutations in this gene have been associated with alternating hemiplegia of childhood-2 (AHC). AHC is a rare neurodevelopmental disorder characterized by hemiplegia, dystonia, cognitive impairment, developmental delays, chorea, and seizures. The E815K mutation is the most severe clinical mutation as well as the second most common mutation associated with AHC. Atp1a3E815K knock-in mice carry the E815K amino acid substitution. Mice heterozygous for Atp1a3E815K develop spontaneous seizures as early as the first few days of life, as well as at P21 to P28. The mutation is lethal in the homozygous state. Changes in environment (new cages, handling) increase the seizure (and mortality) incidence. Mice require fewer electrical stimulations to reach the kindled state. Mice have a high incidence of mortality especially in the second quarter of life and no mice have survived beyond 264 days. Treatment with flunarizine (used to treat AHC) reduces the number of hemiplegic attacks. Atp1a3E815K female mice are smaller in size than males and wild type littermates, although both sexes are smaller at wean age. In addition, mice have varying degrees of impaired episodic memory (novel object recognition test), decreased exploratory behavior, reduced locomotor activity, hind-limb clasping (tail suspension), abnormal gait, paroxysmal dystonia and hemiplegia (forced swim test/water submersion), and perturbed vestibular responses. These mice may be useful in studying alternating hemiplegia of childhood (AHC).
 Of note, Atp1a3E815K mice on a B6C3F1 mixed background are distributed as <a href="https://www.jax.org/strain/038457">RRID:MMRRC_071376-JAX</a>. The B6C3F1 mixed background has a less severe phenotype.

Atp1a3E815K knock-in mice carry a E815K amino acid substitution of the ATPase, Na+/K+ transporting, alpha 3 polypeptide or Matb. Heterozygous mice exhibit early onset spontaneous hemiplegia or seizures. The E815K mutation is lethal in homozygotes. These mice may be useful in studying alternating hemiplegia of childhood (AHC).
 Of note, Atp1a3E815K mice on a B6C3F1 mixed background are distributed as <a href="https://www.jax.org/strain/038457">RRID:MMRRC_071376-JAX</a>. The B6C3F1 mixed background has a less severe phenotype.

This strain is hosted by NIH's MMRRC, which partners with JAX for the distribution of this and other strains. For additional information and to purchase, please visit the MMRRC site.