Vitebsky A, Reyes R, Sanderson M J, Michel W C, Whitlock K E
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Dev Dyn. 2005 Sep;234(1):229-42. doi: 10.1002/dvdy.20530.
To initiate a genetic analysis of olfactory development and function in the zebrafish, Danio rerio, we developed a behavioral genetic screen for mutations affecting the olfactory sensory system. First, we characterized olfactory responses of wild-type zebrafish to various odors. We found that 3-day-old juvenile zebrafish reacted to the amino acid L-cysteine with an aversive behavioral response. We isolated one mutant, laure (lre), which showed no aversive behavioral response to L-cysteine at 3 days of development, and carried out a preliminary characterization of this mutant's defects. We found that lre mutant fish were also defective in their response to L-serine and L-alanine, but not to taurocholic acid, as young adults. In addition, lre mutant fish had significantly fewer primary olfactory sensory neurons than normal, and the axons of these neurons did not form the characteristic axon termination pattern in the developing olfactory bulb. Nevertheless, the olfactory epithelium of lre mutant fish showed normal or near normal electrophysiological responses to several odorants. Our data suggest that the behavioral defects observed in the lre mutant result from the disruption of the developing olfactory sensory neurons and their axonal connections within the olfactory bulb. The isolation of the lre mutant shows that our behavior-based screen represents a viable approach for carrying out a genetic dissection of olfactory behaviors in this vertebrate model system.
为了对斑马鱼（Danio rerio）的嗅觉发育和功能进行遗传分析，我们开发了一种行为遗传学筛选方法，用于筛选影响嗅觉感觉系统的突变。首先，我们对野生型斑马鱼对各种气味的嗅觉反应进行了表征。我们发现3天大的幼年斑马鱼对氨基酸L-半胱氨酸会产生厌恶行为反应。我们分离出一个突变体，名为laure（lre），它在发育3天时对L-半胱氨酸没有厌恶行为反应，并对该突变体的缺陷进行了初步表征。我们发现，lre突变体成年鱼对L-丝氨酸和L-丙氨酸的反应也存在缺陷，但对牛磺胆酸没有缺陷。此外，lre突变体鱼的初级嗅觉感觉神经元明显少于正常鱼，并且这些神经元的轴突在发育中的嗅球中没有形成特征性的轴突终止模式。然而，lre突变体鱼的嗅觉上皮对几种气味剂表现出正常或接近正常的电生理反应。我们的数据表明，在lre突变体中观察到的行为缺陷是由于发育中的嗅觉感觉神经元及其在嗅球内的轴突连接受到破坏所致。lre突变体的分离表明，我们基于行为的筛选方法是在这个脊椎动物模型系统中对嗅觉行为进行遗传剖析的一种可行方法。
