Neonatal motor functions in Cacna1a-mutant rolling Nagoya mice.
Rolling Nagoya mice show ataxia and carry a mutation in the Cacna1a gene, which encodes the pore-forming alpha1 subunit of the Cav2.1 channels. Because an impaired motor function has not been examined during neonatal stages in detail, we employed a battery of tests including assessments of body weight gain, righting reflex, negative geotaxis, hind-limb suspension, and tail suspension using neonatal wild-type, heterozygous, and homozygous rolling mice. We found deterioration of body weight gain after postnatal day 8 (P8) in the homozygous mice, as well as a longer latency time to complete the righting reflex and the negative geotaxis tests after P8. Additionally, the homozygous rolling mice exhibited lower pulling and holding attempts after P8 in the hind-limb suspension test. The mice heterozygous and homozygous for the rolling mutation exhibited muscle fatigue after P10 and P8, respectively, following movement execution tests administered immediately after the first trial, suggesting that gene dosage plays an important role in determining when muscle weakness occurs. The homozygous rolling mice showed hind-limb clasping or touching after P14 during the hind-limb and tail suspension tests. Our results indicate that the gait abnormality of neonatal rolling Nagoya would be due to the combination of muscle weakness and neuronal dysfunction and that the rolling mice could be a useful model for delineating neonatal motor deficiencies.
Takahashi
Eiki
E
Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. etakahashi@brain.riken.jp
Niimi
Kimie
K
Itakura
Chitoshi
C
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type / Q000235:genetics / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D018763:Muscle Fatigue / Q000235:genetics / Q000502:physiology; D009154:Mutation; D013647:Task Performance and Analysis; D013997:Time Factors
D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type