QTL and systems genetics analysis of mouse grooming and behavioral responses to novelty in an open field
Genes, Brain and Behavior. 2017-06-22; :
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1. Genes Brain Behav. 2017 Nov;16(8):790-799. doi: 10.1111/gbb.12392. Epub 2017 Jun
QTL and systems genetics analysis of mouse grooming and behavioral responses to
novelty in an open field.
Delprato A(1)(2)(3), Algéo MP(1)(2), Bonheur B(1)(2), Bubier JA(4), Lu L(5),
Williams RW(5), Chesler EJ(4), Crusio WE(1)(2).
(1)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, University
of Bordeaux, Pessac, France.
(2)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS,
(3)BioScience Project, Wakefield, MA, USA.
(4)The Jackson Laboratory, Bar Harbor, ME, USA.
(5)Department of Genetics, Genomics and Informatics, University of Tennessee
Health Sciences Center, Memphis, TN, USA.
The open field is a classic test used to assess exploratory behavior, anxiety and
locomotor activity in rodents. Here, we mapped quantitative trait loci (QTLs)
underlying behaviors displayed in an open field, using a panel of 53 BXD
recombinant inbred mouse strains with deep replication (10 per strain and sex).
The use of these strains permits the integration and comparison of data obtained
in different laboratories, and also offers the possibility to study trait
covariance by exploiting powerful bioinformatics tools and resources. We
quantified behavioral traits during 20-min test sessions including (1) percent
time spent and distance traveled near the wall (thigmotaxis), (2) leaning against
the wall, (3) rearing, (4) jumping, (5) grooming duration, (6) grooming
frequency, (7) locomotion and (8) defecation. All traits exhibit moderate
heritability making them amenable to genetic analysis. We identified a
significant QTL on chromosome M.m. 4 at approximately 104 Mb that modulates
grooming duration in both males and females (likelihood ratio statistic values of
approximately 18, explaining 25% and 14% of the variance, respectively) and a
suggestive QTL modulating locomotion that maps to the same locus. Bioinformatic
analysis indicates Disabled 1 (Dab1, a key protein in the reelin signaling
pathway) as a particularly strong candidate gene modulating these behaviors. We
also found 2 highly suggestive QTLs for a sex by strain interaction for grooming
duration on chromosomes 13 and 17. In addition, we identified a pairwise
epistatic interaction between loci on chromosomes 12 at 36-37 Mb and 14 at
34-36 Mb that influences rearing frequency in males.
© 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics
PMCID: PMC5800503 [Available on 2018-11-01]
PMID: 28544613 [Indexed for MEDLINE]