Host genetics maps to behaviour and brain structure in developmental mice

• Published in: Behavioral and brain functions Vol. 21; no. 1; pp. 1 - 20
• Main Authors: Asbury, Sarah, Lai, Jonathan K. Y., Rilett, Kelly C., Haqqee, Zeeshan, Darwin, Benjamin C., Ellegood, Jacob, Lerch, Jason P., Foster, Jane A.
• Format: Journal Article
• Language: English
• Published: England BioMed Central 02.01.2025; BMC
• Subjects: Anatomy; Animals; Behavior, Animal - physiology; Brain - growth & development; Brain architecture; Communication; Design of experiments; Digitization; Early life stress; Female; Gene mapping; Gene-Environment Interaction; Genetics; Genotype; Genotypes; Machine learning; Male; Mice; Mice, Inbred C57BL; Neurodevelopment; Neuroimaging; Phenotype; Phenotypes; Phenotyping; Postpartum period; Random forest; Structural MRI; T cell receptors; Volumetric analysis; Neurodevelopment; Structural MRI; Early life stress; Random forest; Machine learning
• ISSN: 1744-9081; 1744-9081
• 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.