Absence of deficits in social behaviors and ultrasonic vocalizations in later generations of mice lacking neuroligin4.
Absence of deficits in social behaviors and ultrasonic vocalizations in later generations of mice lacking neuroligin4.
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DOI：
10.1111/j.1601-183x.2012.00849.x
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发表时间：
2012-11
期刊：
影响因子：
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通讯作者：
Crawley JN
中科院分区：
文献类型：
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作者：
Ey E;Yang M;Katz AM;Woldeyohannes L;Silverman JL;Leblond CS;Faure P;Torquet N;Le Sourd AM;Bourgeron T;Crawley JN
NLGN 4X的突变已经在患有自闭症谱系障碍和其他神经发育障碍的个体中被鉴定。先前的一项研究报告说，缺乏神经胶质素4（Nlgn 4）的成年雄性小鼠在三腔测试中表现出社会接近缺陷，改变了攻击行为，减少了超声发声。为了复制和扩展这些发现，在美国马里兰州贝塞斯达的国家精神卫生研究所和法国巴黎的巴斯德研究所，对同一系Nlgn 4突变小鼠的后代进行了孤独症相关行为表型的独立综合分析。在两个地点测试的所有三种基因型的Nlgn 4小鼠中，成年人的社交方式是正常的。青少年的互惠社会互动在不同基因型中也是同样正常的。没有检测到基因型差异在超声波发声的幼崽从巢或成人在相互的社会互动。在不同基因型之间，类似行为、自我梳理、旋转棒和开阔场地探索没有差异，发育里程碑和一般健康状况的测量结果也正常。我们的研究结果表明在两个地点测试的Nlgn 4小鼠的后代中缺乏自闭症相关的行为表型。测试环境和方法在某些方面与原始研究不同，尽管在所有基因型中都存在正常的社交能力。从这项研究中获得的不同结果表明，表型可能无法在繁殖世代之间复制，并强调了环境，世代和/或程序因素对行为表型的重要作用。
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 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.