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Contrasting characteristic behaviours among common laboratory mouse strains.

ABSTRACT: Mice are widely used to model wide-ranging human neurological disorders, from development to degenerative pathophysiology. Behavioural and molecular characteristics of these mouse models are influenced by the genetic background of each strain. Among the most commonly used strains, the inbred C57BL/6J, BALB/c, CBA and 129SvEv lines and the CD1 outbred line are particularly predominant. Despite their prevalence, comparative performance of these strains on many standard behavioural tests commonly used to assess neurological conditions remains diffusely and indirectly accessible in the literature. Given that independent studies may be conducted with mice of differing genetic backgrounds, any variation in characteristic behavioural responses of specific strains should be delineated in order to properly interpret results among studies. Thus, in the present study, we aimed to characterize these commonly used mice strains through several standard behavioural tests. Here, we found that animals from different genetic background strains exhibited varying behavioural patterns when assessed for sociability/novelty, memory function, and negative behaviours like despair and stress calls. These results suggest that genetic variation among strains may be responsible-in part-for strain-specific behavioural phenotypes and potential predisposition to some neurological disorders.

SUBMITTER: Sultana R

PROVIDER: S-EPMC6599779 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Contrasting characteristic behaviours among common laboratory mouse strains.

Sultana Razia R Ogundele Olalekan M OM Lee Charles C CC

Royal Society open science 20190612 6

Mice are widely used to model wide-ranging human neurological disorders, from development to degenerative pathophysiology. Behavioural and molecular characteristics of these mouse models are influenced by the genetic background of each strain. Among the most commonly used strains, the inbred C57BL/6J, BALB/c, CBA and 129SvEv lines and the CD1 outbred line are particularly predominant. Despite their prevalence, comparative performance of these strains on many standard behavioural tests commonly u ...[more]

PMID: 31312505

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Project description:BackgroundGenetic variation in a population has an influence on the manifestation of monogenic as well as multifactorial disorders, with the underlying genetic contribution dependent on several interacting variants. Common laboratory mouse strains used for modelling human disease lack the genetic variability of the human population. Therefore, outcomes of rodent studies show limited relevance to human disease. The functionality of brain vasculature is an important modifier of brain diseases. Importantly, the restrictive interface between blood and brain-the blood-brain barrier (BBB) serves as a major obstacle for the drug delivery into the central nervous system (CNS). Using genetically diverse mouse strains, we aimed to investigate the phenotypic and transcriptomic variation of the healthy BBB in different inbred mouse strains.MethodsWe investigated the heterogeneity of brain vasculature in recently wild-derived mouse strains (CAST/EiJ, WSB/EiJ, PWK/PhJ) and long-inbred mouse strains (129S1/SvImJ, A/J, C57BL/6J, DBA/2J, NOD/ShiLtJ) using different phenotypic arms. We used immunohistochemistry and confocal laser microscopy followed by quantitative image analysis to determine vascular density and pericyte coverage in two brain regions-cortex and hippocampus. Using a low molecular weight fluorescence tracer, sodium fluorescein and spectrophotometry analysis, we assessed BBB permeability in young and aged mice of selected strains. For further phenotypic characterization of endothelial cells in inbred mouse strains, we performed bulk RNA sequencing of sorted endothelial cells isolated from cortex and hippocampus.ResultsCortical vessel density and pericyte coverage did not differ among the investigated strains, except in the cortex, where PWK/PhJ showed lower vessel density compared to NOD/ShiLtJ, and a higher pericyte coverage than DBA/2J. The vascular density in the hippocampus differed among analyzed strains but not the pericyte coverage. The staining patterns of endothelial arteriovenous zonation markers were similar in different strains. BBB permeability to a small fluorescent tracer, sodium fluorescein, was also similar in different strains, except in the hippocampus where the CAST/EiJ showed higher permeability than NOD/ShiLtJ. Transcriptomic analysis of endothelial cells revealed that sex of the animal was a major determinant of gene expression differences. In addition, the expression level of several genes implicated in endothelial function and BBB biology differed between wild-derived and long-inbred mouse strains. In aged mice of three investigated strains (DBA/2J, A/J, C57BL/6J) vascular density and pericyte coverage did not change-expect for DBA/2J, whereas vascular permeability to sodium fluorescein increased in all three strains.ConclusionsOur analysis shows that although there were no major differences in parenchymal vascular morphology and paracellular BBB permeability for small molecular weight tracer between investigated mouse strains or sexes, transcriptomic differences of brain endothelial cells point to variation in gene expression of the intact BBB. These baseline variances might be confounding factors in pathological conditions that may lead to a differential functional outcome dependent on the sex or genetic polymorphism.

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Contrasting characteristic behaviours among common laboratory mouse strains.

Publications

Contrasting characteristic behaviours among common laboratory mouse strains.

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