Chromosomal Assignment of Quantitative Trait Loci Influencing Modified Hole Board Behavior in Laboratory Mice using Consomic Strains, with Special Reference to Anxiety-related Behavior and Mouse Chromosome 19

Laarakker, Marijke C.; Ohl, Frauke; Lith, H.A. van

doi:10.1007/s10519-007-9188-6

Cited by 24 publications

(47 citation statements)

References 39 publications

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“…Thus a high anxiety characteristic might not necessarily be detrimental to an animal's state of welfare as long as an individual is able to adapt, resulting in a decrease in anxiety towards a specific challenge over time [4], [6], [8]. Given that the process of selection and inbreeding in laboratory mice has resulted in the (unintentional) co-selection of emotional traits (see for example [8], [11], [13], [14], [44], [45]), we hypothesize that standard housing and treatment protocols for mice as a species may be insufficient to safeguard the welfare of different mouse (sub)strains equally. Compared to other strains, different 129 substrains reveal a reduced ability to adapt to exposure to novelty.…”

Section: Discussionmentioning

confidence: 99%

Not All Mice Are Equal: Welfare Implications of Behavioural Habituation Profiles in Four 129 Mouse Substrains

et al. 2012

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Safeguarding the welfare of animals is an important aim when defining housing and management standards in animal based, experimental research. While such standards are usually defined per animal species, it is known that considerable differences between laboratory mouse strains exist, for example with regard to their emotional traits. Following earlier experiments, in which we found that 129P3 mice show a lack of habituation of anxiety related behaviour after repeated exposure to an initially novel environment (non-adaptive profile), we here investigated four other 129 inbred mouse substrains (129S2/SvPas, 129S2/SvHsd (exp 1); 129P2 and 129X1 (exp 2)) on habituation of anxiety related behaviour. Male mice of each strain were repeatedly placed in the modified hole board test, measuring anxiety-related behaviour, exploratory and locomotor behaviour. The results reveal that all four substrains show a lack of habituation behaviour throughout the period of testing. Although not in all of the substrains a possible confounding effect of general activity can be excluded, our findings suggest that the genetic background of the 129 substrains may increase their vulnerability to cope with environmental challenges, such as exposure to novelty. This vulnerability might negatively affect the welfare of these mice under standard laboratory conditions when compared with other strains. Based on our findings we suggest to consider (sub)strain-specific guidelines and protocols, taking the (subs)train-specific adaptive capabilities into account.

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Section: Discussionmentioning

confidence: 99%

Not All Mice Are Equal: Welfare Implications of Behavioural Habituation Profiles in Four 129 Mouse Substrains

et al. 2012

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“…The QTL on chromosome 4 has been identified previously as relevant to activity. This chromosome has been identified in a number of open‐field activity studies (Gill & Boyle 2005; Henderson et al 2004; Laarakker et al 2008; Singer et al 2005; Turri et al 2001a,b). Although the experimental differences between arenas used in this and the other studies might determine the presence or absence of some QTL, finding a common QTL across multiple studies suggests a particularly robust genetic pleiotropy at this locus.…”

Section: Discussionmentioning

confidence: 99%

“…It is widely recognized that a multifactorial etiology underlies rodent behavior in short‐term ethological tests (Archer 1973; Blizard et al 2007; Stanford 2007; Takahashi et al 2006). Consistent with such complexity, quantitative trait locus (QTL) studies with mice have identified a polygenic system using a variety of test instruments (Caldarone et al 1997; Flint et al 1995; Gill & Boyle 2005; Henderson et al 2004; Laarakker et al 2008; Singer et al 2005; Turri et al 2001a,b), and attempts have been made to associate individual QTL with specific biobehavioral processes (Turri et al 2001a).…”

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confidence: 99%

“…Most previous studies have been limited to observations of behaviors in a single test, or multiple tests conducted at closely spaced intervals, and therefore have not addressed the issue of the stability of QTL across moderate spans of time (Caldarone et al 1997; Flint et al 1995; Gill & Boyle 2005; Henderson et al 2004; Laarakker et al 2008; Singer et al 2005; Turri et al 2001b). In the present study, we administered tests of exploration in a hole‐board apparatus, also known as a File Box (File & Wardill 1975), at three time‐points (TP), separated from each other by a 1‐month interval.…”

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Genetic architecture for hole‐board behaviors across substantial time intervals in young, middle‐aged and old mice

Foreman¹,

Lionikas²,

Lang³

et al. 2009

Genes Brain and Behavior

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A quantitative trait locus (QTL) analysis of behaviors across the life span was conducted in F 2 mice from a C57BL/6J × DBA/2J cross and 22 BXD recombinant inbred (RI) strains. Mice of three age groups were tested in a hole-board apparatus for 3 min on three occasions ∼1 month apart (average age at test 150, 450 and 750 days, ∼400 mice per group, divided equally by sex). Quantitative trait loci with small effect size were found on 11 chromosomes for hole-board activity (Hbact) and hole-board rearing (Hbrear). Analysis of 22 RI strains tested at 150 and 450 days of age found only suggestive linkage, with four QTL for Hbact overlapping with those from the F 2 analysis. There was a significant phenotypic correlation between Hbact and Hbrear (∼0.55-0.69) and substantial commonality among QTL for the two behaviors. QTL analyses of head-pokes (HP) and fecal boli (FB) only identified QTL at the suggestive level of significance. Age accounted for ∼15% of the phenotypic variance (sex ∼3%), and there were genotype by age interactions at ∼25% of the Hbact and Hbrear QTL. Quantitative trait loci for Hbrear were relatively stable across the three measurement occasions (those for Hbact somewhat less so), although mean levels of each index declined markedly comparing the first to subsequent trials. Considered as a whole, the polygenic system influencing exploratory behaviors accounts for approximately the same amount of phenotypic variance as age (within the range studied), is stable across substantial periods of time, and acts, for the most part, independently of age and sex.

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“…In addition, Laarakker et al's study [26] reporting a contribution of the Y NPAR to anxiety-related behavior in mice, strengthens the hypothesis of an effect of the Y NPAR or brain BE, given that BE is considered as a stress hormone [27]–[29].…”

Section: Introductionmentioning

confidence: 75%

Modulation of Brain β-Endorphin Concentration by the Specific Part of the Y Chromosome in Mice

et al. 2011

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BackgroundSeveral studies in animal models suggest a possible effect of the specific part of the Y-chromosome (YNPAR) on brain opioid, and more specifically on brain β-endorphin (BE). In humans, male prevalence is found in autistic disorder in which observation of abnormal peripheral or central BE levels are also reported. This suggests gender differences in BE associated with genetic factors and more precisely with YNPAR.Methodology/Principal FindingsBrain BE levels and plasma testosterone concentrations were measured in two highly inbred strains of mice, NZB/BlNJ (N) and CBA/HGnc (H), and their consomic strains for the YNPAR. An indirect effect of the YNPAR on brain BE level via plasma testosterone was also tested by studying the correlation between brain BE concentration and plasma testosterone concentration in eleven highly inbred strains. There was a significant and major effect (P<0.0001) of the YNPAR in interaction with the genetic background on brain BE levels. Effect size calculated using Cohen's procedure was large (56% of the total variance). The variations of BE levels were not correlated with plasma testosterone which was also dependent of the YNPAR.Conclusions/SignificanceThe contribution of YNPAR on brain BE concentration in interaction with the genetic background is the first demonstration of Y-chromosome mediated control of brain opioid. Given that none of the genes encompassed by the YNPAR encodes for BE or its precursor, our results suggest a contribution of the sex-determining region (Sry, carried by YNPAR) to brain BE concentration. Indeed, the transcription of the Melanocortin 2 receptor gene (Mc2R gene, identified as the proopiomelanocortin receptor gene) depends on the presence of Sry and BE is derived directly from proopiomelanocortin. The results shed light on the sex dependent differences in brain functioning and the role of Sry in the BE system might be related to the higher frequency of autistic disorder in males.

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Chromosomal Assignment of Quantitative Trait Loci Influencing Modified Hole Board Behavior in Laboratory Mice using Consomic Strains, with Special Reference to Anxiety-related Behavior and Mouse Chromosome 19

Cited by 24 publications

References 39 publications

Not All Mice Are Equal: Welfare Implications of Behavioural Habituation Profiles in Four 129 Mouse Substrains

Not All Mice Are Equal: Welfare Implications of Behavioural Habituation Profiles in Four 129 Mouse Substrains

Genetic architecture for hole‐board behaviors across substantial time intervals in young, middle‐aged and old mice

Modulation of Brain β-Endorphin Concentration by the Specific Part of the Y Chromosome in Mice

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