Examining litter specific variability in mice and its impact on neurodevelopmental studies
Vanessa Valiquette,
Elisa Guma,
Lani Cupo,
Daniel Gallino,
Chloe Anastassiadis,
Emily Snook,
Gabriel A. Devenyi,
M. Mallar Chakravarty
Affiliations
Vanessa Valiquette
Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada; Computional Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada; Corresponding authors.
Elisa Guma
Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada; Computional Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada; Section On Developmental Neurogenomics, National Institute of Mental Health, Bethesda, MD, USA
Lani Cupo
Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada; Computional Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada
Daniel Gallino
Computional Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada
Chloe Anastassiadis
Computional Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada; Institute of Medical Science & Collaborative Program in Neuroscience, University of Toronto, Toronto, ON, Canada
Emily Snook
Computional Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada
Gabriel A. Devenyi
Computional Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada; Department of Psychiatry, McGill University, Montreal, QC, Canada
M. Mallar Chakravarty
Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada; Computional Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada; Department of Psychiatry, McGill University, Montreal, QC, Canada; Department of Biology and Biomedical Engineering, McGill University, Montreal, QC, Canada; Corresponding authors.
Our current understanding of litter variability in neurodevelopmental studies using mice may limit translation of neuroscientific findings. Higher variance of measures across litters than within, often termed intra-litter likeness, may be attributable to both pre- and postnatal environment. This study aimed to assess the litter-effect within behavioral assessments (2 timepoints) and anatomy using T1-weighted magnetic resonance images across 72 brain region volumes (4 timepoints) (36 C57bl/6J inbred mice; 7 litters: 19F/17M). Between-litter comparisons of brain and behavioral measures and their associations were evaluated using univariate and multivariate techniques. A power analysis using simulation methods was then performed on modeled neurodevelopment and to evaluate trade-offs between number-of-litters, number-of-mice-per-litter, and sample size. Our results show litter-specific developmental effects, from the adolescent period to adulthood for brain structure volumes and behaviors, and for their associations in adulthood. Our power simulation analysis suggests increasing the number-of-litters in experimental designs to achieve the smallest total sample size necessary for detecting different rates of change in specific brain regions. Our results demonstrate how litter-specific effects may influence development and that increasing the litters to the total sample size ratio should be strongly considered when designing neurodevelopmental studies.
