Use of SHIRPA and discriminant analysis to characterise marked differences in the behavioural phenotype of six inbred mouse strains

Rogers, Derek C.; Jones, Declan N.C.; Nelson, Paul R.; Jones, Cynthia M.; Quilter, Charlotte A.; Robinson, Tracy; Hagan, Jim J.

doi:10.1016/s0166-4328(99)00072-8

Cited by 266 publications

(202 citation statements)

References 27 publications

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“…control) DBA/2 mice displayed greater avoidance of open arms and, thus, higher levels of anxiety than C57BL/6 mice, which is in accordance with previous observations (Crawley et al, 1997;Griebel et al, 1997;Ohl et al, 2003;Rodgers et al, 1999). On the neuroendocrine level, previous studies reported a significant increase in plasma corticosterone after EPM exposure (File et al, 1994;Holmes et al, 1998).…”

Section: Article In Presssupporting

confidence: 90%

The temporal dynamics of intrahippocampal corticosterone in response to stress-related stimuli with different emotional and physical load: An in vivo microdialysis study in C57BL/6 and DBA/2 inbred mice

Thoeringer

Sillaber²,

Roedel

et al. 2007

Psychoneuroendocrinology

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SummaryThere is strong evidence for a pivotal interaction of corticosteroid signalling and behavioral adaptation to stress. To further elucidate this relation, we monitored the dynamics of free corticosterone in the murine hippocampus of two inbred mouse strains using in vivo microdialysis. C57BL/6JOlaHsd (C57BL/6) and DBA/2OlaHsd (DBA/2) inbred mouse strains have been shown to differ in their anxiety-related and depression-like behavior and provide, thus, an interesting animal model to study the stimulus-response profile of the hypothalamus-pituitary-adrenocortical (HPA) system as a function of emotional and physical load. We, first, compared peripheral and intracerebral concentration patterns of corticosterone by simultaneous microdialysis of the jugular vein and the hippocampus in anesthetized mice and found strain differences in blood versus intracerebral free corticosterone concentrations. C57BL/6 showed almost the same steroid levels in either compartment, whereas DBA/2 mice displayed higher glucocorticoid levels in the circulation than in the hippocampus. This data suggest a strain difference in the tissue environment influencing the amount of biological active corticosterone at the receptor site. Measurements of intrahippocampal corticosterone in freely moving mice revealed that DBA/2 display a prolonged glucocorticoid increase in response to a single forced swimming stress (FST), as compared to C57BL/6 mice indicating a reduced inhibitory HPA axis feedback. Exposure to a novel environment (NE) induced a desensitization of the HPA system in DBA/2 animals as they show an attenuated intracerebral corticosterone dynamics after a subsequent FST. Testing animals in an elevated plus-maze (EPM), however, did not significantly stimulate coriticosterone release in either strain. The analysis of the area under the curve revealed a high amount of corticosterone released through FST and a low glucocorticoid release after NE or EPM exposure that are independent of the strain. This data indicate a strong stimulus dependency of corticosterone secretion that is strain independent, whereas the dynamics and feedback of the HPA axis is different between both inbred strains. Behavioral phenotyping of animals revealed a strong impact of microdialysis procedure on FST and EPM performance. Innate emotionality differences of both strains, however, were not affected. Though descriptive in nature, the present results suggest an altered corticosteroid signalling in the DBA/2 strain compared to C57BL/6 mice. Whether this observation causally underlies the differences in anxiety-related and depression-like behavior has to be further experimentally validated. In addition, our study highlights the use of in vivo microdialysis to assess the neuroendocrine endophenotype of animal models via profiling of stimulus-response patterns of stress hormones. ARTICLE IN PRESS

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Section: Article In Presssupporting

confidence: 90%

The temporal dynamics of intrahippocampal corticosterone in response to stress-related stimuli with different emotional and physical load: An in vivo microdialysis study in C57BL/6 and DBA/2 inbred mice

Thoeringer

Sillaber²,

Roedel

et al. 2007

Psychoneuroendocrinology

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“…There were generally similar extents of habituation in each wildtype group for behaviours such as locomotion, rearing to wall, grooming, and sifting, indicating little influence of genetic background (C57BL/6 vs 129/Sv Â C57BL/6) on these topographies. However, habituation of behaviours such as sniffing and rearing free was slower in C57BL/6 than in 129/Sv Â C57BL/ 6 wildtypes; while this might appear consistent with evidence suggesting reduced 'activity' in the 129/Sv strain (Rogers et al, 1999;Carter et al, 2001;Ralph et al, 2001), the present data indicate this to be a topographically specific rather than any generalised effect. More fundamentally, the extent of retardation of habituation in congenic D 1A mutants was substantially greater than that in D 1A mutants on a mixed background even on taking differences between wildtype profiles into account; thus, it was possible to demonstrate large time (0-370 min) Â genotype (D1A-null vs wildtype) Â background (congenic C57BL/6 vs mixed 129/Sv Â C57BL/6) interactions on contrasting the present data with our previous data obtained in the same laboratory using identical experimental procedures Waddington et al, 2001).…”

Section: Congenic D 1a Knockout Phenotypesupporting

confidence: 87%

Congenic D1A Dopamine Receptor Mutants: Ethologically Based Resolution of Behavioural Topography Indicates Genetic Background as a Determinant of Knockout Phenotype

McNamara

Clifford

Tighe

et al. 2002

Neuropsychopharmacol

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D 1A -null mice were backcrossed over 14 generations into a C57BL/6 background to result in essential elimination (to o0.005%) of any contribution from the 129/Sv component of their initially mixed (129/Sv Â C57BL/6) background. Their phenotype was assessed using an ethologically based approach that resolves each individual topography of behaviour in the natural repertoire. Habituation of sniffing, locomotion, rearing seated, and rearing to wall in wild types over several hours was profoundly retarded in congenic D 1A mutants; conversely, rearing free and sifting were essentially abolished. Resultant increases in individual topographies of behaviour were substantially greater in congenic D 1A mutants than in those on a mixed background. This phenotype was little altered by the selective

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“…Discrepancy of findings may be greater in tests related to anxiety-like behavior [47]. Some strain comparisons have suggested that DBA/2J mice are characterized by anxietyrelated responses and high or intermediate-high emotional reactivity [16,41,45]. In the present study, the DBA/2J strain had the lowest level of time spent in the center of the activity chamber.…”

Section: Discussionmentioning

confidence: 38%

Social approach and repetitive behavior in eleven inbred mouse strains

Moy

Nadler

Young³

et al. 2008

Behavioural Brain Research

222

211

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Core symptoms of autism include deficits in social interaction, impaired communication, and restricted, repetitive behaviors. The repetitive behavior domain encompasses abnormal motoric stereotypy, an inflexible insistence on sameness, and resistance to change. In recent years, many genetic mouse models of autism and related disorders have been developed, based on candidate genes for disease susceptibility. The present studies are part of an ongoing initiative to develop appropriate behavioral tasks for the evaluation of mouse models relevant to autism. We have previously reported profiles for sociability, preference for social novelty, and resistance to changes in a learned pattern of behavior, as well as other functional domains, for 10 inbred mouse strains of divergent genetic backgrounds. The present studies extend this multi-component behavioral characterization to several additional strains: C58/J, NOD/LtJ, NZB/B1NJ, PL/J, SJL/J, SWR/J, and the wild-derived PERA/ EiJ. C58/J, NOD/LtJ, NZB/B1NJ, SJL/J, and PERA/EiJ demonstrated low sociability, measured by time spent in proximity to an unfamiliar conspecific, with 30% to 60% of mice from these strains showing social avoidance. In the Morris water maze, NZB/B1NJ had a persistent bias for the quadrant where the hidden platform was located during acquisition, even after nine days of reversal training. A particularly interesting profile was found for C58/J, which had low social preference, poor performance in the T-maze, and overt motoric stereotypy. Overall, this set of tasks and observational methods provides a strategy for evaluating novel mouse models in behavioral domains relevant to the autism phenotype.

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Use of SHIRPA and discriminant analysis to characterise marked differences in the behavioural phenotype of six inbred mouse strains

Cited by 266 publications

References 27 publications

The temporal dynamics of intrahippocampal corticosterone in response to stress-related stimuli with different emotional and physical load: An in vivo microdialysis study in C57BL/6 and DBA/2 inbred mice

The temporal dynamics of intrahippocampal corticosterone in response to stress-related stimuli with different emotional and physical load: An in vivo microdialysis study in C57BL/6 and DBA/2 inbred mice

Congenic D1A Dopamine Receptor Mutants: Ethologically Based Resolution of Behavioural Topography Indicates Genetic Background as a Determinant of Knockout Phenotype

Social approach and repetitive behavior in eleven inbred mouse strains

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