Abstract
Genetic variation is a primary determinant of phenotypic diversity. In laboratory mice, genetic variation can be a serious experimental confounder, and thus minimized through inbreeding. However, generalizations of results obtained with inbred strains must be made with caution, especially when working with complex phenotypes and disease models. Here we compared behavioral characteristics of C57Bl/6—the strain most widely used in biomedical research—with those of 129S4. In contrast to 129S4, C57Bl/6 demonstrated high within-strain and intra-litter behavioral hyperactivity. Although high consistency would be advantageous, the majority of disease models and transgenic tools are in C57Bl/6. We recently established six Cre driver lines and two Cre effector lines in 129S4. To augment this collection, we genetically engineered a Cre line to study astrocytes in 129S4. It was validated with two Cre effector lines: calcium indicator gCaMP5g-tdTomato and RiboTag—a tool widely used to study cell type-specific translatomes. These reporters are in different genomic loci, and in both the Cre was functional and astrocyte-specific. We found that calcium signals lasted longer and had a higher amplitude in cortical compared to hippocampal astrocytes, genes linked to a single neurodegenerative disease have highly divergent expression patterns, and that ribosome proteins are non-uniformly expressed across brain regions and cell types.
Highlights
Genetic variation is a primary determinant of phenotypic diversity
To compare behavioral characteristics of B6 and S4 strains, we performed automated mouse behavior analysis (AMBA) using videos of mice in standard cages recorded for 24-h periods every 2 months starting at 6 months of age
Much of the hyper-repetitive behaviors occurred during the dark cycle, when mice are typically not observed by human investigators (Supplementary Movie S1, https://tinyurl.com/wcmz[9]zf)
Summary
Genetic variation is a primary determinant of phenotypic diversity. In laboratory mice, genetic variation can be a serious experimental confounder, and minimized through inbreeding. Constitutive expression of Cre with astrocyte specific marker genes or promoter elements results in recombination in cells that later become neurons[39,40]. We thought that having a Cre active in a very homogeneous cell type in an accessed brain region would be extremely useful, especially for gene expression studies.
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