Asbury Sarah, Lai Jonathan K Y, Rilett Kelly C, Haqqee Zeeshan, Darwin Benjamin C, Ellegood Jacob, Lerch Jason P, Foster Jane A
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada.
Behav Brain Funct. 2025 Jan 2;21(1):1. doi: 10.1186/s12993-024-00261-y.
Gene-environment interactions in the postnatal period have a long-term impact on neurodevelopment. To effectively assess neurodevelopment in the mouse, we developed a behavioural pipeline that incorporates several validated behavioural tests to measure translationally relevant milestones of behaviour in mice. The behavioral phenotype of 1060 wild type and genetically-modified mice was examined followed by structural brain imaging at 4 weeks of age. The influence of genetics, sex, and early life stress on behaviour and neuroanatomy was determined using traditional statistical and machine learning methods. Analytical results demonstrated that neuroanatomical diversity was primarily associated with genotype whereas behavioural phenotypic diversity was observed to be more susceptible to gene-environment variation. We describe a standardized mouse phenotyping pipeline, termed the Developmental Behavioural Milestones (DBM) Pipeline released alongside the 1000 Mouse Developmental Behavioural Milestones (1000 Mouse DBM) database to institute a novel framework for reproducible interventional neuroscience research.
出生后时期的基因-环境相互作用对神经发育具有长期影响。为了有效评估小鼠的神经发育,我们开发了一种行为流程,该流程纳入了多项经过验证的行为测试,以测量小鼠行为中与转化相关的里程碑。对1060只野生型和转基因小鼠的行为表型进行了检查,随后在4周龄时进行了脑结构成像。使用传统统计方法和机器学习方法确定了基因、性别和早期生活压力对行为和神经解剖结构的影响。分析结果表明,神经解剖结构的多样性主要与基因型相关,而行为表型的多样性则更容易受到基因-环境变异的影响。我们描述了一种标准化的小鼠表型分析流程,称为发育行为里程碑(DBM)流程,该流程与1000个小鼠发育行为里程碑(1000 Mouse DBM)数据库一起发布,以建立一个用于可重复干预神经科学研究的新框架。