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bioRxiv · 10.1101/2022.09.09.506402

Examining Litter Specific Variability in Mice and its Impact on Neurodevelopmental Studies

Valiquette, V.·Guma, E.·Cupo, L.·Gallino, D.·Anastassiadis, C.·Snook, E.·Devenyi, G. A.·Chakravarty, M. M.
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Abstract

Our current understanding of litter variability in neurodevelopmental studies using mouse may limit translation of neuroscientific findings. Higher variance of measures across litters than within, often termed intra-litter likeness, may be attributable to 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 (4 timepoints) across 72 brain region volumes (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 modeling neurodevelopment and evaluating trade-offs between number-of-litters, 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 their associations in adulthood. Our power simulation analysis results suggest increasing the number-of-litters in experimental design to achieve the smallest total sample size for detecting different rates of change in specific brain regions. Our results also 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.

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Valiquette, V., Guma, E., Cupo, L., Gallino, D., Anastassiadis, C., Snook, E., Devenyi, G. A., Chakravarty, M. M.. 2022-09-10. Examining Litter Specific Variability in Mice and its Impact on Neurodevelopmental Studies. https://doi.org/10.1101/2022.09.09.506402

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