Lijam N, Paylor R, McDonald M P, Crawley J N, Deng C X, Herrup K, Stevens K E, Maccaferri G, McBain C J, Sussman D J, Wynshaw-Boris A
Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cell. 1997 Sep 5;90(5):895-905. doi: 10.1016/s0092-8674(00)80354-2.
Mice completely deficient for Dvl1, one of three mouse homologs of the Drosophila segment polarity gene Dishevelled, were created by gene targeting. Dvl1-deficient mice are viable, fertile, and structurally normal. Surprisingly, these mice exhibited reduced social interaction, including differences in whisker trimming, deficits in nest-building, less huddling contact during home cage sleeping, and subordinate responses in a social dominance test. Sensorimotor gating was abnormal, as measured by deficits in prepulse inhibition of acoustic and tactile startle. Thus, Dvl1 mutants may provide a model for aspects of several human psychiatric disorders. These results are consistent with an interpretation that common genetic mechanisms underlie abnormal social behavior and sensorimotor gating deficits and implicate Dvl1 in processes underlying complex behaviors.
通过基因打靶技术构建了完全缺失果蝇节段极性基因“凌乱”（Dishevelled）的三个小鼠同源物之一Dvl1的小鼠。Dvl1基因缺失的小鼠能够存活、繁殖，且结构正常。令人惊讶的是，这些小鼠表现出社交互动减少，包括胡须修剪差异、筑巢缺陷、在饲养笼中睡眠时的抱团接触减少，以及在社会优势测试中的从属反应。感觉运动门控异常，通过对听觉和触觉惊吓的前脉冲抑制缺陷来衡量。因此，Dvl1突变体可能为几种人类精神疾病的某些方面提供一个模型。这些结果与一种解释一致，即异常的社会行为和感觉运动门控缺陷背后存在共同的遗传机制，并表明Dvl1参与了复杂行为的潜在过程。
