IMPC phenotypes (gene matching)
B6.129S1-Atp1a3Myk/StclH
| Status | Available to order |
| EMMA ID | EM:15264 |
| International strain name | B6.129S1-Atp1a3Myk/StclH |
| Alternative name | B6.129S1-Atp1a3 Myk/Stcl (a.k.a. Myshkin) |
| Strain type | Induced Mutant Strains : Chemically-induced |
| Allele/Transgene symbol | Atp1a3Myk |
| Gene/Transgene symbol | Atp1a3 |
Information from provider
| Provider | Steven Clapcote |
| Provider affiliation | School of Biomedical Sciences, University of Leeds |
| Genetic information | ENU mutagenesis induced point mutations in Atp1a3 exons 3 and 17 that encode amino acid substitutions D65E and I810N. The I810N mutation alone inactivates Na+/K+ ATPase α3. |
| Phenotypic information | Homozygous:Homozygous mice are neonatal lethal. When bred to homozygosity, pups appear grossly normal but die shortly after birth.Heterozygous:Adult heterozygous mice have a 16-18% reduction in body weight compared to wild-type mice. Heterozygotes also exhibit an elevated metabolic rate, a visible whole-body tremor and a broad-based gait, as well as spontaneous and vestibular stress-induced seizures, medial temporal sclerosis, sleep abnormalities, and a variety of motor, cognitive, social and other behavioural deficits (reviewed in Ng HWY et al., 2021, doi:10.1242/dmm.048938). |
| Breeding history | The mutation was induced by ENU in a 129S1/SvImJ mouse and was first detected within that mouse's (C57BL/6J × 129S1/SvImJ) F1 progeny. The line was maintained by backcrossing heterozygous males to C57BL/6NCr (NCI, Frederick) females for 20 generations. Atp1a3Myk heterozygous males were then backcrossed two generations with C57BL/6JCrl females (Charles River). The line is currently maintained by breeding wild-type females from the colony with heterozygous males. |
| References |
|
| Homozygous fertile | no |
| Homozygous viable | no |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Mary Lyon Centre at MRC Harwell, Oxford, United Kingdom |
Disease and phenotype information
Orphanet associated rare diseases, based on orthologous gene matching
- Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome / Orphanet_1171
- Rapid-onset dystonia-parkinsonism / Orphanet_71517
- Alternating hemiplegia of childhood / Orphanet_2131
- Non-specific early-onset epileptic encephalopathy / Orphanet_442835
MGI phenotypes (gene matching)
- tremors / MGI
- paralysis / MGI
- abnormal temporal lobe morphology / MGI
- abnormal dentate gyrus morphology / MGI
- convulsive seizures / MGI
- decreased body weight / MGI
- decreased body size / MGI
- decreased anxiety-related response / MGI
- ataxia / MGI
- hyperactivity / MGI
- hypoactivity / MGI
- impaired coordination / MGI
- abnormal gait / MGI
- short stride length / MGI
- decreased exploration in new environment / MGI
- abnormal spatial learning / MGI
- abnormal startle reflex / MGI
- abnormal sleep pattern / MGI
- limb grasping / MGI
- increased thermal nociceptive threshold / MGI
- seizures / MGI
- abnormal motor capabilities/coordination/movement / MGI
- premature death / MGI
- abnormal CNS synaptic transmission / MGI
- abnormal respiratory function / MGI
- abnormal sensorimotor gating / MGI
- increased thigmotaxis / MGI
- abnormal long term object recognition memory / MGI
- increased susceptibility to pharmacologically induced seizures / MGI
- astrocytosis / MGI
- abnormal response to novel object / MGI
- nervous system phenotype / MGI
- enhanced coordination / MGI
- impaired passive avoidance behavior / MGI
- abnormal neuron physiology / MGI
- abnormal behavior / MGI
- dystonia / MGI
- homeostasis/metabolism phenotype / MGI
- growth/size/body region phenotype / MGI
- behavior/neurological phenotype / MGI
- abnormal action potential / MGI
- abnormal enzyme/coenzyme activity / MGI
- abnormal spike wave discharge / MGI
- abnormal xenobiotic pharmacokinetics / MGI
- microgliosis / MGI
- decreased prepulse inhibition / MGI
- abnormal seizure response to inducing agent / MGI
- environmentally induced seizures / MGI
- abnormal miniature inhibitory postsynaptic currents / MGI
- impaired contextual conditioning behavior / MGI
- enhanced conditioned place preference behavior / MGI
- enhanced behavioral response to addictive substance / MGI
- increased sensitivity to xenobiotic induced morbidity/mortality / MGI
- abnormal hippocampus granule cell morphology / MGI
- abnormal hippocampus pyramidal cell morphology / MGI
- neonatal lethality, complete penetrance / MGI
- preweaning lethality, incomplete penetrance / MGI
- abnormal habituation / MGI
- abnormal habituation to a new environment / MGI
- abnormal sensitization to xenobiotic / MGI
- decreased frequency of paradoxical sleep / MGI
- abnormal paradoxical sleep pattern / MGI
- abnormal non-rapid eye movement sleep pattern / MGI
- impaired spatial learning / MGI
- increased kindling response / MGI
- prolonged circadian behavior period / MGI
Literature references
- Deficits in social behavioral tests in a mouse model of alternating hemiplegia of childhood.;Kirshenbaum Greer S, Idris Nagi F, Dachtler James, Roder John C, Clapcote Steven J, ;2016;Journal of neurogenetics;30;42-9; 27276195
- Genetic suppression of agrin reduces mania-like behavior in Na+ , K+ -ATPase α3 mutant mice.;Kirshenbaum G S, Clapcote S J, Petersen J, Vilsen B, Ralph M R, Roder J C, ;2012;Genes, brain, and behavior;11;436-43; 22520507
- Characterization of cognitive deficits in mice with an alternating hemiplegia-linked mutation.;Kirshenbaum Greer S, Dachtler James, Roder John C, Clapcote Steven J, ;2015;Behavioral neuroscience;129;822-31; 26501181
- Transgenic rescue of phenotypic deficits in a mouse model of alternating hemiplegia of childhood.;Kirshenbaum Greer S, Dachtler James, Roder John C, Clapcote Steven J, ;2016;Neurogenetics;17;57-63; 26463346
- Mutation I810N in the alpha3 isoform of Na+,K+-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS.;Clapcote Steven J, Duffy Steven, Xie Gang, Kirshenbaum Greer, Bechard Allison R, Rodacker Schack Vivien, Petersen Janne, Sinai Laleh, Saab Bechara J, Lerch Jason P, Minassian Berge A, Ackerley Cameron A, Sled John G, Cortez Miguel A, Henderson Jeffrey T, Vilsen Bente, Roder John C, ;2009;Proceedings of the National Academy of Sciences of the United States of America;106;14085-90; 19666602
- Alternating hemiplegia of childhood-related neural and behavioural phenotypes in Na+,K+-ATPase α3 missense mutant mice.;Kirshenbaum Greer S, Dawson Neil, Mullins Jonathan G L, Johnston Tom H, Drinkhill Mark J, Edwards Ian J, Fox Susan H, Pratt Judith A, Brotchie Jonathan M, Roder John C, Clapcote Steven J, ;2013;PloS one;8;e60141; 23527305
- Mania-like behavior induced by genetic dysfunction of the neuron-specific Na+,K+-ATPase α3 sodium pump.;Kirshenbaum Greer S, Clapcote Steven J, Duffy Steven, Burgess Christian R, Petersen Janne, Jarowek Karolina J, Yücel Yeni H, Cortez Miguel A, Snead O Carter, Vilsen Bente, Peever John H, Ralph Martin R, Roder John C, ;2011;Proceedings of the National Academy of Sciences of the United States of America;108;18144-9; 22025725
- Circadian Disruptions in the Myshkin Mouse Model of Mania Are Independent of Deficits in Suprachiasmatic Molecular Clock Function.;Timothy Joseph W S, Klas Natasza, Sanghani Harshmeena R, Al-Mansouri Taghreed, Hughes Alun T L, Kirshenbaum Greer S, Brienza Vincent, Belle Mino D C, Ralph Martin R, Clapcote Steven J, Piggins Hugh D, ;2018;Biological psychiatry;84;827-837; 28689605