Within-strain variation in behavior differs consistently between common inbred strains of mice

Abstract

Genetic and environmental factors interact throughout life and give rise to individual differences, i.e., individuality. The diversifying effect of environmental factors is counteracted by genetic mechanisms to yield persistence of specific features (robustness). Here, we compared robustness between cohorts of isogenic mice of eight different commonly used strains by analyzing to what extent environmental variation contributed to individuality in each of the eight genotypes, using a previously published dataset. Behavior was assessed in the home-cage, providing control over environmental factors, to reveal within-strain variability in numerous spontaneous behaviors. Indeed, despite standardization and in line with previous studies, substantial variability among mice of the same inbred strain was observed. Strikingly, across a multidimensional set of 115 behavioral parameters, several strains consistently ranked high in within-strain variability (DBA/2J, 129S1/Sv A/J and NOD/LtJ), whereas other strains ranked low (C57BL/6J and BALB/c). Strain rankings of within-strain variability in behavior were confirmed in an independent, previously published behavioral dataset using conventional behavioral tests administered to different mice from the same breeding colonies. Together, these show that genetically inbred mouse strains consistently differ in phenotypic robustness against environmental variation, suggesting that genetic factors contribute to variation in robustness.

A murine model of peripheral irradiation-induced fatigue

“…Post-irradiation cumulative VWRA distance in kilometers was less in mice irradiated with 800 cGy (n=4, 111.9 ± 10.3) compared to those irradiated with 600 cGy (n=4, 116.8 ± 17.9) and to non-irradiated mice (n=3, 148.2 ± 68.0) (Figure 1A). There was considerable variability in VWRA distance in the second pilot trial, which may be related to the small number of mice, as well as to unseen environmental and genetic factors [33–35]. All mice were observed to be in good health throughout this trial.…”

On the Digital Psychopharmacology of Valproic Acid in Mice

“…In this study, we asked whether detailed automated evaluations of home-cage behavior would be sensitive enough to detect anticonvulsant psychotropic effects, and further, reveal features of pervasive neurodevelopment (if any) in mice exposed to that anticonvulsant prenatally. We chose VPA as a prototypical AED known to display both such features, and employed C57BL/6J mice as subjects, given their widely reproducible home-cage ethograms 32,50,67 and low rates of within-strain variability 68 . Home-cage monitoring is grounded on the assumption that if a rodent were to experience clinically meaningful symptoms of autism, developmental delay, anxiety or depression, such a syndrome would exert measurable effects on activities of daily living as measured in their home-cages.…”

Home-cage Monitoring Ascertains Signatures of Ictal and Interictal Behavior In Mouse Models of Generalized Seizures

“…In this study, we utilize an established home-cage monitoring platform (28,29) to obtain objective and unbiased continuous measures of ictal and spontaneous interictal murine behavior with negligible human presence in three distinct mouse models. With PTZ injections, we demonstrate how acute convulsive severity is independent and distinct from "behavioral" severity.…”