TY - JOUR
T1 - Motor coordination impairment in aged heterozygous rolling Nagoya, Cav2.1 mutant mice
AU - Takahashi, Eiki
AU - Niimi, Kimie
AU - Itakura, Chitoshi
N1 - Funding Information:
The rolling Nagoya mouse strain was found among descendants of a cross between the SIII and C57BL/6 strains and has been maintained by intercross mating ( Oda, 1973 ). The rolling Nagoya mouse strain was provided by the RIKEN BioResource Center, with support from the National BioResource Project of the Ministry of Education, Culture, Sports, Science and Technology, Japan. Male homozygous (rol/rol) and heterozygous (rol/+) rolling mice and male wild-type (+/+) mice that were F1 progeny from a cross between rol/+ mice (SIII × C57BL/6 background) were used as our previous reports ( Takahashi and Niimi, 2009; Takahashi et al., 2009 ). Genotypes were identified by PCR of DNA from tail biopsies of 3-week-old mice according to our previous report ( Takahashi and Niimi, 2009 ). Two-month-old (young, 5–8 weeks old) and 22-month-old (aged, 85–88 weeks old) mice were used. Immediately after they were genotyped, the mice were assigned randomly to group housing (n = 5 per cage; floor space, 17 × 27 × 13 cm; microisolation cage; Allentown Caging Equipment, Allentown, NJ, USA). The mice were given free access to water and food pellets (CRF-1; Oriental Yeast Co., Ltd., Tokyo, Japan) and were kept at room temperature (23 ± 1 °C) and 55 ± 5% humidity under a controlled 12/12-h light–dark cycle (lights on from 08:00 to 20:00). We examined body weight in young and aged +/+, rol/+ and rol/rol mice (young +/+, rol/+, rol/rol, n = 10 each; aged +/+, rol/+, rol/rol, n = 10 each). All behavioral analyses were conducted between 09:00 and 16:00 by a well trained experimenter who was blinded to the mouse strains. The mice were moved into the behavioral testing room at least 1 h prior to testing. All animal procedures were approved by the Animal Experiments Committee of RIKEN, and all animals were cared for and treated humanely in accordance with the Institutional Guidelines for Experiments Using Animals.
PY - 2009/7/7
Y1 - 2009/7/7
N2 - Although rolling Nagoya mice exhibit ataxia and carry a mutation in the α1 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 α1 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 α1 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 Cav2.1α1 mRNA was lower in aged mice than in young mice and that mutant-type Cav2.1α1 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.
AB - Although rolling Nagoya mice exhibit ataxia and carry a mutation in the α1 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 α1 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 α1 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 Cav2.1α1 mRNA was lower in aged mice than in young mice and that mutant-type Cav2.1α1 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.
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U2 - 10.1016/j.brainres.2009.05.016
DO - 10.1016/j.brainres.2009.05.016
M3 - Article
C2 - 19446536
AN - SCOPUS:67649403105
SN - 0006-8993
VL - 1279
SP - 50
EP - 57
JO - Molecular Brain Research
JF - Molecular Brain Research
ER -