Pleiotropic effects of a disrupted K+channel gene: Reduced body weight, impaired motor skill and muscle contraction, but no seizures
- 18 February 1997
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 94 (4) , 1533-1538
- https://doi.org/10.1073/pnas.94.4.1533
Abstract
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.Keywords
This publication has 22 references indexed in Scilit:
- Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmiasNature Genetics, 1996
- Hereditary nondystrophic myotonias and periodic paralysesCurrent Opinion in Neurology, 1995
- Assembly of Voltage-gated Potassium ChannelsPublished by Elsevier ,1995
- A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndromeCell, 1995
- Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1Nature Genetics, 1994
- GABA‐Ergic interneurons of the striatum express the shaw‐like potassium channel KvS3.1Synapse, 1994
- Alternative splicing contributes to K+ channel diversity in the mammalian central nervous system.Proceedings of the National Academy of Sciences, 1991
- Potassium channels from NG108‐15 neuroblastoma‐glioma hybrid cellsFEBS Letters, 1989
- A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloningNature, 1989
- Performance of normal and neurological mutant mice on radial arm maze and active avoidance tasksBehavioral and Neural Biology, 1986