Motor coordination impairment in aged heterozygous rolling Nagoya, Cav2.1 mutant mice.
Although rolling Nagoya mice exhibit ataxia and carry a mutation in the alpha1 subunit of the Cav2.1 channel regulating neurotransmitter release, heterozygous mice have not received a great deal of attention. Given the pivotal role of Cav2.1 channels in controlling neurotransmitter release, age-dependent alterations in Cav2.1 channel function may result in aberrant synaptic signaling, leading to motor dysfunction. To examine age-related motor alterations in heterozygous mice, we used a battery of tests (e.g., motor activity, footprint, traction, wire suspension, balance beam, rotating rod, hind-limb extension analysis) in 2- and 22-month-old mice and examined expression patterns of the alpha1 gene in their cerebellum. No significant difference was observed between 2-month-old heterozygous and wild-type mice in the any of the behavioral tests or in the alpha1 expression levels. Although 22-month-old heterozygous and wild-type mice exhibited no significant difference in motor activity, footprint, or traction tests, 22-month-old heterozygous mice showed deficits in the wire hanging, balance beam, and rotating rod tests. Additionally, 22-month-old heterozygous mice displayed clasping behavior in the hind-limb extension test. Expression analysis showed that wild-type Cav2.1alpha(1) mRNA was lower in aged mice than in young mice and that mutant-type Cav2.1alpha(1) mRNA was higher in aged mice than in young mice. These findings suggest that heterozygous mice show age-related motor changes due to mutant-type Cav2.1 and that heterozygous mice may represent a new model for examining motor function.
Takahashi
Eiki
E
Research Resources Center, RIKEN Brain Science Institute, Wako, Saitama, Japan. etakahashi@brain.riken.jp
Niimi
Kimie
K
Itakura
Chitoshi
C
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type / Q000235:genetics* / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000235:genetics* / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000235:genetics*; D009069:Movement Disorders / Q000235:genetics*; D009483:Neuropsychological Tests; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D012333:RNA, Messenger