Pleiotropic effects of a disrupted K+ channel gene: Reduced body weight, impaired motor skill and muscle contraction, but no seizures
Pleiotropic effects of a disrupted K+ channel gene: Reduced body weight, impaired motor skill and muscle contraction, but no seizures
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DOI：
10.1073/pnas.94.4.1533
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发表时间：
1997-02-18
影响因子：
11.1
通讯作者：
Joho, RH
中科院分区：
文献类型：
--
作者：
Ho, CS;Grange, RW;Joho, RH
为了研究K+通道在细胞兴奋性调控和微调中的作用，我们培育了一只携带快速激活、电压门控的K+通道Kv3.1基因的突变小鼠。与Kv3.1（+/-）小鼠相比，Kv3.1（-/-）小鼠可存活和生育，但体重明显减少。野生型、杂合型和纯合型Kv3.1通道缺陷小鼠表现出相似的自发运动和探索活动。然而，在协调运动技能测试中，纯合子Kv3.1（-/-）小鼠的表现明显低于杂合子Kv3.1（+/-）或野生型小鼠。Kv3.1（-/-）小鼠的快骨骼肌和慢骨骼肌在达到峰值力和收缩后放松的速度较慢，因此在较低的刺激频率下导致强直反应，两种突变肌肉在单次抽搐和强直条件下产生明显较小的收缩力。尽管Kv3.1（-/-）突变体表现出正常的听觉频率范围，但它们在声惊吓反应方面表现出显著差异。与预期相反，纯合子Kv3.1（-/-）小鼠没有增加自发癫痫活动。
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.