Mouse Genome Informatics
hm
    Cacna1atm1Maag/Cacna1atm1Maag
B6.129P2-Cacna1atm1Maag
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Neurological deficits after spreading depression in Cacna1atm1Maag/Cacna1atm1Maag and Cacna1atm3Maag/Cacna1atm3Maag mice

nervous system
• mice show increased vulnerability to ischemic stroke, developing an earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations after filament occlusion of the middle cerebral artery associated with rapid expansion of infarct core on diffusion-weighted magnetic resonance imaging
• transient filament occlusion of the middle cerebral artery for 1 hour produces larger infarcts than in wild-type mice, with more severe cortical involvement
• following induction with KCl, spreading depression frequency and propagation speed are increased, especially in females, compared to in wild-type mice but not as much as in Cacna1atm1Caya homozygotes
• ovariectomy and cessation of estrous cycling eliminates sex differences
• however, recovery of cortical evoked potentials after KCl-induced spreading depression is normal
• KCl-induced cortical spreading depression propagates into the striatum unlike in wild-type mice but with lesser frequency and longer latencies than in Cacna1atm1Caya homozygotes
• corticaostriatal propogation of KCl-induced cortical spreading depression is greater in female mice than in male mice
• mice exhibit 1 or more recurrent spreading depressions following brief topical KCl application and extensive washing unlike in wild-type mice

behavior/neurological
• topical application of 300 mM KCl induces a single spreading depression that causes hemiplegia, leaning, circling, and impaired coordination unlike in similarly treated wild-type mice
• a single spreading depression induced by KCl causes hemiplegia with leaning and circling unlike in wild-type mice
• a single spreading depression induced by KCl causes hemiplegia with leaning and circling unlike in wild-type mice
• a single spreading depression induced by KCl causes hemiplegia with leaning and circling unlike in wild-type mice

homeostasis/metabolism
• topical application of 300 mM KCl induces a single spreading depression that causes hemiplegia, leaning, circling, and impaired coordination unlike in similarly treated wild-type mice
• however, recovery of cortical evoked potentials after KCl-induced spreading depression is normal
• KCl-induced cortical spreading depression propagates into the striatum unlike in wild-type mice but with lesser frequency and longer latencies than in Cacna1atm1Caya homozygotes
• corticaostriatal propogation of KCl-induced cortical spreading depression is greater in female mice than in male mice
• mice exhibit 1 or more recurrent spreading depressions following brief topical KCl application and extensive washing unlike in wild-type mice
• mice show increased vulnerability to ischemic stroke, developing an earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations after filament occlusion of the middle cerebral artery associated with rapid expansion of infarct core on diffusion-weighted magnetic resonance imaging
• transient filament occlusion of the middle cerebral artery for 1 hour produces larger infarcts than in wild-type mice, with more severe cortical involvement

Mouse Models of Human Disease
OMIM IDRef(s)
Migraine, Familial Hemiplegic, 1; FHM1 141500 J:144701 , J:193793