Pleiotropic effects of a disrupted K+ channel gene: reduced body weight, impaired motor skill and muscle contraction, but no seizures.
To investigate the roles of K+ channels in the regulation and fine-tuning of cellular excitability, we generated a mutant mouse carrying a disrupted gene for the fast activating, voltage-gated K+ channel Kv3.1. Kv3.1-/- mice are viable and fertile but have significantly reduced body weights compared with their Kv3.1+/- littermates. Wild-type, heterozygous, and homozygous Kv3.1 channel-deficient mice exhibit similar spontaneous locomotor and exploratory activity. In a test for coordinated motor skill, however, homozygous Kv3.1-/- mice perform significantly worse than their heterozygous Kv3.1+/- or wild-type littermates. Both fast and slow skeletal muscles of Kv3.1-/- mice are slower to reach peak force and to relax after contraction, consequently leading to tetanic responses at lower stimulation frequencies. Both mutant muscles generate significantly smaller contractile forces during a single twitch and during tetanic conditions. Although Kv3.1-/- mutants exhibit a normal auditory frequency range, they show significant differences in their acoustic startle responses. Contrary to expectation, homozygous Kv3.1-/- mice do not have increased spontaneous seizure activity.
Ho
C S
CS
Department of Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center, Dallas 75235-9111, USA.
Grange
R W
RW
Joho
R H
RH
D000367:Age Factors; D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D001835:Body Weight; D005260:Female; D006720:Homozygote; D008124:Locomotion; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009048:Motor Skills; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000502:physiology; D016296:Mutagenesis; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015221:Potassium Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D013216:Reflex, Startle; D012640:Seizures; D012727:Sex Characteristics; D051670:Shaw Potassium Channels
D009479:Neuropeptides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051670:Shaw Potassium Channels