Ey E, Yang M, Katz A M, Woldeyohannes L, Silverman J L, Leblond C S, Faure P, Torquet N, Le Sourd A-M, Bourgeron T, Crawley J N
Human Genetics and Cognitive Functions, URA 2182 'Genes, synapses and cognition', Institut Pasteur, Paris, France.
CNRS, URA 2182 'Genes, synapses and cognition', Institut Pasteur, Paris, France.
Genes Brain Behav. 2012 Nov;11(8):928-941. doi: 10.1111/j.1601-183X.2012.00849.x. Epub 2012 Oct 10.
Mutations in NLGN4X have been identified in individuals with autism spectrum disorders and other neurodevelopmental disorders. A previous study reported that adult male mice lacking neuroligin4 (Nlgn4) displayed social approach deficits in the three-chambered test, altered aggressive behaviors and reduced ultrasonic vocalizations. To replicate and extend these findings, independent comprehensive analyses of autism-relevant behavioral phenotypes were conducted in later generations of the same line of Nlgn4 mutant mice at the National Institute of Mental Health in Bethesda, MD, USA and at the Institut Pasteur in Paris, France. Adult social approach was normal in all three genotypes of Nlgn4 mice tested at both sites. Reciprocal social interactions in juveniles were similarly normal across genotypes. No genotype differences were detected in ultrasonic vocalizations in pups separated from the nest or in adults during reciprocal social interactions. Anxiety-like behaviors, self-grooming, rotarod and open field exploration did not differ across genotypes, and measures of developmental milestones and general health were normal. Our findings indicate an absence of autism-relevant behavioral phenotypes in subsequent generations of Nlgn4 mice tested at two locations. Testing environment and methods differed from the original study in some aspects, although the presence of normal sociability was seen in all genotypes when methods taken from Jamain et al. (2008) were used. The divergent results obtained from this study indicate that phenotypes may not be replicable across breeding generations, and highlight the significant roles of environmental, generational and/or procedural factors on behavioral phenotypes.
在患有自闭症谱系障碍和其他神经发育障碍的个体中已发现NLGN4X基因突变。先前的一项研究报告称，成年雄性neuroligin4（Nlgn4）基因敲除小鼠在三室试验中表现出社交接近缺陷、攻击行为改变以及超声波发声减少。为了重复和扩展这些发现，美国马里兰州贝塞斯达国家心理健康研究所和法国巴黎巴斯德研究所对同一品系的Nlgn4突变小鼠的后代进行了与自闭症相关行为表型的独立综合分析。在两个研究地点测试的所有三种Nlgn4小鼠基因型中，成年小鼠的社交接近行为均正常。不同基因型的幼年小鼠之间的相互社交互动同样正常。在与巢穴分离的幼崽或成年小鼠相互社交互动期间的超声波发声中，未检测到基因型差异。焦虑样行为、自我梳理、转棒试验和旷场探索在不同基因型之间没有差异，发育里程碑和总体健康指标也正常。我们的研究结果表明，在两个地点测试的Nlgn4小鼠后代中不存在与自闭症相关的行为表型。尽管采用Jamain等人（2008年）的方法时在所有基因型中都观察到了正常的社交能力，但测试环境和方法在某些方面与原研究不同。本研究获得的不同结果表明，表型可能无法在不同繁殖代之间重复，并突出了环境、代际和/或程序因素对行为表型的重要作用。
