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. On this STOCK background, which segregates the C57BL/6 and C3H genomes (as well as some 129), mice exhibit a less severe phenotype than the C57BL/6 congenic background (MMRRC Stock No. <a href="https://www.jax.org/strain/036936">069591</a>). Of 200 heterozygous mice aged to 11 weeks, no mice have exhibited seizures or have died. In addition, female mice are smaller in size than wildtype or males, both sexes exhibit a slight tremor and dystonia at 6 weeks of age with a 70% penetrance. It is assumed that the mutation is lethal in the homozygous state, although it has not yet been tested. Update May, 2025: Some heterozygous mice in our colony exhibit a severe tremor phenotype by ~6 weeks of age. A shortened lifespan (10-12 weeks) has been noted in some animals. Short snouts and an overall runted appearance are also observed. On the congenic C57BL/6 background, 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. C57BL/6 mice require fewer electrical stimulations to reach the kindled state. C57BL/6 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 on the C57BL/6 backgorund. 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 the C57BL/6 congenic background are distributed as <a href="https://www.jax.org/strain/036936">RRID:MMRRC_069591-JAX</a>. The C57BL/6 congenic background has a more severe phenotype.

Atp1a3E815K knock-in mice carry a E815K amino acid substitution of the ATPase, Na+/K+ transporting, alpha 3 polypeptide or Matb. The E815K mutation is lethal in homozygotes. These mice may be useful in studying alternating hemiplegia of childhood (AHC). Of note, Atp1a3E815K mice on the C57BL/6 congenic background are distributed as <a href="https://www.jax.org/strain/036936">RRID:MMRRC_069591-JAX</a>. The C57BL/6 congenic background has a more 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.