High-throughput behavioral phenotyping in the expanded panel of BXD recombinant inbred strains.

paper Cited Public

Authors: Philip, V M; Duvvuru, S; Gomero, B; Ansah, T A; Blaha, C D; Cook, M N; Hamre, K M; Lariviere, W R; Matthews, D B; Mittleman, G; Goldowitz, D; Chesler, E J
Year: 2010
Journal: Genes, brain, and behavior
PMID: 19958391
DOI: 10.1111/j.1601-183X.2009.00540.x
PMCID: PMC2855868

Figure 1

Strain intra-class correlations for all measures. (a) Frequency histogram of strain intra-class correlations for both sexes combined. A majority of the behavioral measures (146 of 257) have ω2 greater than 30% making them amenable to QTL mapping. (b) Scatter plot of strain intra-class correlations for males and females. Dotted lines are 95% upper and lower prediction intervals for the relationship between these values. Dashed lines are the corresponding 95% upper and lower confidence intervals.

LLM interpretation

This figure consists of two panels analyzing strain intra-class correlations ($\omega^2$). Panel (a) is a frequency histogram showing the distribution of $\omega^2$ for both sexes combined, with a peak count between 30% and 40%. Panel (b) is a scatter plot comparing $\omega^2$ values between males (x-axis) and females (y-axis), featuring a positive linear trend with associated 95% prediction intervals (dotted lines) and confidence intervals (dashed lines).

Figure 2

Quantitative trait locus analysis of mechanical nociception in the original and recent BXD RI panels: QTL analysis of a single-trait, the latency to respond to a plastic-coated smooth alligator clip placed on the tail was performed across three BXD panels, namely, Taylor I (BXD 1–32), Recent BXD RI (BXD 33–100) and Full BXD RI (BXD 1–100). In females, suggestive QTL were detected on Chr 1 and 9 for Taylor I (a), Chr 8 for the Recent BXD RI (BXD 33–100) (b) and Chr 1, 11 and 17 for the Full RI Lines (c). Mapping of tail clip latency in males showed no suggestive QTL for Taylor I (d), suggestive QTL on Chr 2, 9 and 18 for Recent BXD RI (BXD 33–100) (e), and two suggestive QTL on Chr 2 and 9 for the Full RI panel (f).

LLM interpretation

This figure consists of three Manhattan plots (d, e, and f) showing quantitative trait locus (QTL) analysis for tail clip latency in male mice across three BXD panels: Taylor I, Recent RI, and Full RI. The x-axes represent genomic position in megabases across chromosomes 1–19 and X, while the y-axes measure the LOD score. Peaks indicating suggestive QTL are visible on chromosomes 2, 9, and 18 for the Recent RI panel (e), and on chromosomes 2 and 9 for the Full RI panel (f), whereas no suggestive QTL are observed for the Taylor I panel (d).

Figure 3

Effect plot of marker gnf01.018.340 (Chr 1 at 21.43 Mb) in Taylor I (BXD 1–32) and Recent RI (BXD 33–100). The marker present at the suggestive QTL in Taylor 1 has a higher phenotypic means for the B allele when compared with the D allele. This difference is significant and therefore results in the presence of a QTL. The same marker in the Recent BXD RI lines has a higher phenotypic mean for the D allele, but no QTL is present within this strain set.

LLM interpretation

This is a line graph showing the phenotypic means for two genotype groups (BB and DD) across two different strain sets. For the Taylor I group (dashed line), the BB genotype has a higher phenotypic mean than the DD genotype, whereas for the Recent BXD RI group (solid line), the DD genotype has a higher mean than the BB genotype. The y-axis represents the "Phenotypic Mean" and the x-axis represents "Genotypes."

Figure 4

Factor scores from individual strains plotted on a set of axes each representing a factor show a behavioral profile of each strain. Although some strains exhibit different magnitudes of similar profiles, others are distinct. Axes labels represent the first eight factors: (1) injection stress-induced locomotor activity, (2) morphine withdrawal (3) morphine response, (4) reactivity, (5) locomotor activity in a novel environment, (6) conflict avoidance, (7) morphine activity duration and (8) cocaine sensitization. All strain profiles are available in supplementary figure.

LLM interpretation

This figure consists of a series of radar (spider) plots showing behavioral factor scores for 12 different BXD mouse strains. Each plot features eight axes representing distinct behavioral factors, ranging from (1) injection stress-induced locomotor activity to (8) cocaine sensitization. The plots illustrate varying behavioral profiles across strains, with some showing similar shapes but different magnitudes and others exhibiting distinct patterns.

Figure 5

Across trait and across studies correlations: (a) saline-induced locomotor activity: in our study two laboratories, Memphis (Cocaine) and UTHSC (Ethanol), collected data on open field locomotion following saline in 15 and 20 min on 64 BXD RI strains, respectively. We compared these data with data collected on saline-induced locomotor response by Demarest et al. (1999) on 25 BXD RI strains. Results indicate that there is good correlation among data on saline-induced locomotor response across the laboratories and to a previously published study. Correlations among the rMemphis,UTHSC = 0.556,rMemphis,Demarest = 0.781 and rDemarest,UTHSC = 0.695. (b) Thermal nociception: thermal nociception (hot plate latency) was preformed in two laboratories, namely, ORNL and Memphis in this study. Data collected in this study were compared with a previously published study of thermal nociception by Mogil et al. (1997) and Brigman et al. (2009). Correlations ranged from 0.274 to 0.799 (Fig. 4b). The low correlation among the data collected at the Memphis and ORNL laboratories may be attributed to the two different hot plate temperatures used.

LLM interpretation

This figure consists of two correlation matrices (a and b) featuring scatter plots and histograms. Panel (a) shows correlations for saline-induced locomotor activity across three groups (Demarest et al., Memphis, and UTHSC), with Pearson correlation coefficients ($r$) ranging from 0.654 to 0.783. Panel (b) displays correlations for thermal nociception across four groups (Memphis, ORNL, Mogil et al., and Brigman et al.), with $r$ values ranging from 0.274 to 0.799. Each matrix displays the distribution of individual traits as histograms along the diagonal and the relationship between pairs as scatter plots with associated $r$ and $N$ values.

#	Section	Preview
80	Results — Finding multi-dimensional extreme strains	percent time in center of open field) and BXD 99 (high for percent time spent in open quadrant,…
81	Results — Integrating data across phenotypic batteries and comparisons to previously published studies	The multi-variate phenotypes measured in this study were obtained from multiple test batteries that…
82	Results — Integrating data across phenotypic batteries and comparisons to previously published studies — Saline-induced locomotor response	Locomotor activity in an open field has been commonly used as a measure for exploration, novelty…
83	Results — Integrating data across phenotypic batteries and comparisons to previously published studies — Thermal nociception	Sensitivity to thermal stimuli is a complex trait that has been used as a predictor of sensitivity…
84	Results — Integrating data across phenotypic batteries and comparisons to previously published studies — Thermal nociception	the Mogil study compared with the Memphis hot plate data. This is likely due to the 54°C that was…
85	Results — Integrating data across phenotypic batteries and comparisons to previously published studies — Thermal nociception	It should be noted that for all the above stated results, comparisons were effectively between data…
86	Results — Combinatorial analysis of gene–phenotype associations	GeneNetwork analysis of each trait resulted in the generation of over 3500 sets of genes that are…
87	Results — Combinatorial analysis of gene–phenotype associations	to identify those genes which most broadly and reliably related to the behavioral functions…
88	Results — Combinatorial analysis of gene–phenotype associations	Genes that were highly connected to many of the trait measures were entered into gene set…
89	Discussion	With the increased deployment of systems genetics and the availability of high-throughput molecular…
90	Discussion	Many of the traits in this study are mouse models of behavioral predictors of substance abuse in…
91	Discussion	The majority of the measures we studied are amenable for QTL mapping, as showed by high genetic…
92	Discussion	(2004) showed that maximum similarity between additive QTL effects and the correlation between a…
93	Discussion	Sex differences and sex × strain interactions are found for a majority of the behavioral traits in…
94	Discussion	strain and across sex within each genotype class. The latter approach reduces multiple testing…
95	Discussion	Interestingly, the sex differences we observed were not just in the mean trait values of the two…
96	Discussion	resident intruder paradigm have been shown to affect neurogenesis (Mitra et al. 2006) and…
97	Discussion	Although the expanded BXD set increases the precision of the genetic map, there is concern as to…
98	Discussion	0.39% among polymorphic SNPs. It is predicted that some traits may be affected by these loci,…
99	Discussion	The presence of these recent polymorphisms creates a challenge illustrated by our analysis of the…

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External

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Repeated dosing with cocaine produces strain-dependent effects on responding for conditioned reinforcement in Collaborative Cross mice.	Bailey LS et al.	—	2023	→
The ameliorative effects of choline on ethanol-induced cell death in the neural tube of susceptible BXD strains of mice.	Xu F et al.	—	2023	→
Cocaine-Induced Locomotor Activation Differs Across Inbred Mouse Substrains.	Gaines CH et al.	—	2022	→
Genetic Mapping of Behavioral Traits Using the Collaborative Cross Resource.	Xuan W et al.	—	2022	→
Genome-wide association mapping of ethanol sensitivity in the Diversity Outbred mouse population.	Parker CC et al.	—	2022	→
New Insights on Gene by Environmental Effects of Drugs of Abuse in Animal Models Using GeneNetwork.	Chunduri A et al.	—	2022	→
Zhx2 Is a Candidate Gene Underlying Oxymorphone Metabolite Brain Concentration Associated with State-Dependent Oxycodone Reward.	Beierle JA et al.	—	2022	→
A platform for experimental precision medicine: The extended BXD mouse family.	Ashbrook DG et al.	—	2021	→
BXD Recombinant Inbred Mice as a Model to Study Neurotoxicity.	Martins AC et al.	—	2021	→
Differential effects by sex with Kmt5b loss.	Wickramasekara RN et al.	—	2021	→
Do gene expression findings from mouse models of cocaine use recapitulate human cocaine use disorder in reward circuitry?	Huggett SB et al.	—	2021	→
Genes identified in rodent studies of alcohol intake are enriched for heritability of human substance use.	Huggett SB et al.	—	2021	→
Genetic Modulation of Initial Sensitivity to Δ9-Tetrahydrocannabinol (THC) Among the BXD Family of Mice.	Parks C et al.	—	2021	→
Heritable variation in locomotion, reward sensitivity and impulsive behaviors in a genetically diverse inbred mouse panel.	Bailey LS et al.	—	2021	→
Highlights from the Era of Open Source Web-Based Tools.	Anderson KR et al.	—	2021	→
Integration of evidence across human and model organism studies: A meeting report.	Palmer RHC et al.	—	2021	→
Multi-omic and multi-species meta-analyses of nicotine consumption.	Palmer RHC et al.	—	2021	→
Systems genetic analysis of nicotine withdrawal deficits in hippocampus-dependent learning.	Goldberg LR et al.	—	2021	→
Whole-Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open-Field Activity.	Thomas AL et al.	—	2021	→
Bioinformatics identification and pharmacological validation of Kcnn3/K<sub>Ca</sub>2 channels as a mediator of negative affective behaviors and excessive alcohol drinking in mice.	Padula AE et al.	—	2020	→
Discovery of a Role for <i>Rab3b</i> in Habituation and Cocaine Induced Locomotor Activation in Mice Using Heterogeneous Functional Genomic Analysis.	Bubier JA et al.	—	2020	→
Genetic variation regulates opioid-induced respiratory depression in mice.	Bubier JA et al.	—	2020	→
Machine learning-based automated phenotyping of inflammatory nocifensive behavior in mice.	Wotton JM et al.	—	2020	→
Mouse Systems Genetics as a Prelude to Precision Medicine.	Li H et al.	—	2020	→
Neuroinflammation, Pain and Depression: An Overview of the Main Findings.	Campos ACP et al.	—	2020	→
Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis.	Datta U et al.	—	2020	→
Sex and Strain Variation in Initial Sensitivity and Rapid Tolerance to Δ9-Tetrahydrocannabinol.	Parks C et al.	—	2020	→
Turning strains into strengths for understanding psychiatric disorders.	Moore SJ et al.	—	2020	→
Using a mouse model to gain insights into developmental coordination disorder.	Gill KK et al.	—	2020	→
A Cross-Species Systems Genetics Analysis Links APBB1IP as a Candidate for Schizophrenia and Prepulse Inhibition.	Ashbrook DG et al.	—	2019	→
Discovery of early life stress interacting and sex-specific quantitative trait loci impacting cocaine responsiveness.	Bagley JR et al.	—	2019	→
Exploring the involvement of Tac2 in the mouse hippocampal stress response through gene networking.	Hook M et al.	—	2019	→
Knockdown of heterochromatin protein 1 binding protein 3 recapitulates phenotypic, cellular, and molecular features of aging.	Neuner SM et al.	—	2019	→
Systems genetics of sensation seeking.	Dickson PE et al.	—	2019	→
The other side of the coin: Hypersociability.	Toth M	—	2019	→
An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice.	Metten P et al.	—	2018	→
Born to Cry: A Genetic Dissection of Infant Vocalization.	Ashbrook DG et al.	—	2018	→
Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations and Drinking Behavior.	Cannady R et al.	—	2018	→
Cross-species molecular dissection across alcohol behavioral domains.	Farris SP et al.	—	2018	→
Genetic Contribution to Initial and Progressive Alcohol Intake Among Recombinant Inbred Strains of Mice.	Mulligan MK et al.	—	2018	→
Genetic differences in the behavioral organization of binge eating, conditioned food reward, and compulsive-like eating in C57BL/6J and DBA/2J strains.	Babbs RK et al.	—	2018	→
Genome wide association analysis in a mouse advanced intercross line.	Gonzales NM et al.	—	2018	→
Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma.	King R et al.	—	2018	→
Post-genomic behavioral genetics: From revolution to routine.	Ashbrook DG et al.	—	2018	→
Quantitative trait locus mapping and analysis of heritable variation in affiliative social behavior and co-occurring traits.	Knoll AT et al.	—	2018	→
The role of physical exercise on Sestrin1 and 2 accumulations in the skeletal muscle of mice.	Crisol BM et al.	—	2018	→
Alterations in the expression of a neurodevelopmental gene exert long-lasting effects on cognitive-emotional phenotypes and functional brain networks: translational evidence from the stress-resilient Ahi1 knockout mouse.	Lotan A et al.	—	2017	→
Analyses of differentially expressed genes after exposure to acute stress, acute ethanol, or a combination of both in mice.	Baker JA et al.	—	2017	→
BXD recombinant inbred strains participate in social preference, anxiety and depression behaviors along sex-differences in cytokines and tactile allodynia.	López-Granero C et al.	—	2017	→
Complex Genetics of Behavior: BXDs in the Automated Home-Cage.	Loos M et al.	—	2017	→
Differential potassium channel gene regulation in BXD mice reveals novel targets for pharmacogenetic therapies to reduce heavy alcohol drinking.	Rinker JA et al.	—	2017	→
Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms.	Adkins AE et al.	—	2017	→
Initial genetic dissection of serum neuroactive steroids following chronic intermittent ethanol across BXD mouse strains.	Porcu P et al.	—	2017	→
Orbitofrontal Neuroadaptations and Cross-Species Synaptic Biomarkers in Heavy-Drinking Macaques.	Nimitvilai S et al.	—	2017	→
QTL and systems genetics analysis of mouse grooming and behavioral responses to novelty in an open field.	Delprato A et al.	—	2017	→
Systems Genetic Analysis in GeneNetwork.org.	Parker CC et al.	—	2017	→
Variable effects of chronic intermittent ethanol exposure on ethanol drinking in a genetically diverse mouse cohort.	Lopez MF et al.	—	2017	→
Analysis of morphine responses in mice reveals a QTL on Chromosome 7.	Crusio WE et al.	—	2016	→
A novel heat shock protein alpha 8 (Hspa8) molecular network mediating responses to stress- and ethanol-related behaviors.	Urquhart KR et al.	—	2016	→
Quantitative Trait Loci and a Novel Genetic Candidate for Fear Learning.	Knoll AT et al.	—	2016	→
Systems genetics identifies Hp1bp3 as a novel modulator of cognitive aging.	Neuner SM et al.	—	2016	→
Systems genetics of intravenous cocaine self-administration in the BXD recombinant inbred mouse panel.	Dickson PE et al.	—	2016	→
Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption.	Smith ML et al.	—	2016	→
A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder.	Ashbrook DG et al.	—	2015	→
Association of novelty-related behaviors and intravenous cocaine self-administration in Diversity Outbred mice.	Dickson PE et al.	—	2015	→
GeneWeaver: finding consilience in heterogeneous cross-species functional genomics data.	Bubier JA et al.	—	2015	→
Identification of candidate genes that underlie the QTL on chromosome 1 that mediates genetic differences in stress-ethanol interactions.	Cook MN et al.	—	2015	→
Influence of sex on genetic regulation of "drinking in the dark" alcohol consumption.	Vanderlinden LA et al.	—	2015	→
Linking traits based on their shared molecular mechanisms.	Oren Y et al.	—	2015	→
Prenatal stress and adult drug-seeking behavior: interactions with genes and relation to nondrug-related behavior.	Kippin TE et al.	—	2015	→
Functionally enigmatic genes: a case study of the brain ignorome.	Pandey AK et al.	—	2014	→
Limitation of number of strains and persistence of false positive loci in QTL mapping using recombinant inbred strains.	Wang L et al.	—	2014	→
Out of the bottleneck: the Diversity Outcross and Collaborative Cross mouse populations in behavioral genetics research.	Chesler EJ	—	2014	→
Performance of C57BL/6J and DBA/2J mice on a touchscreen-based attentional set-shifting task.	Dickson PE et al.	—	2014	→
Refinement of experimental design and conduct in laboratory animal research.	Bailoo JD et al.	—	2014	→
Scoring the collective effects of SNPs: association of minor alleles with complex traits in model organisms.	Yuan D et al.	—	2014	→
The circadian clock gene Csnk1e regulates rapid eye movement sleep amount, and nonrapid eye movement sleep architecture in mice.	Zhou L et al.	—	2014	→
The heritability of oxycodone reward and concomitant phenotypes in a LG/J × SM/J mouse advanced intercross line.	Bryant CD et al.	—	2014	→
The α3β4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies.	Muldoon PP et al.	—	2014	→
Unique genetic loci identified for emotional behavior in control and chronic stress conditions.	Carhuatanta KA et al.	—	2014	→
Anxiety genetics - findings from cross-species genome-wide approaches.	Sokolowska E et al.	—	2013	→
Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization.	Adkins DE et al.	—	2013	→
Critical evaluation of transcription factor Atf2 as a candidate modulator of alcohol preference in mouse and human populations.	Wang LS et al.	—	2013	→
Different coexpressions of arthritis-relevant genes between different body organs and different brain regions in the normal mouse population.	Cao Y et al.	—	2013	→
Epigenetic regulation of opioid-induced hyperalgesia, dependence, and tolerance in mice.	Liang DY et al.	—	2013	→
High-precision genetic mapping of behavioral traits in the diversity outbred mouse population.	Logan RW et al.	—	2013	→
Potential role of Atp5g3 in epigenetic regulation of alcohol preference or obesity from a mouse genomic perspective.	Huang Y et al.	—	2013	→
Potential translational targets revealed by linking mouse grooming behavioral phenotypes to gene expression using public databases.	Roth A et al.	—	2013	→
Use of the expanded panel of BXD mice narrow QTL regions in ethanol-induced locomotor activation and motor incoordination.	DuBose CS et al.	—	2013	→
Accelerating discovery for complex neurological and behavioral disorders through systems genetics and integrative genomics in the laboratory mouse.	Bubier JA et al.	—	2012	→
Behavioral actions of alcohol: phenotypic relations from multivariate analysis of mutant mouse data.	Blednov YA et al.	—	2012	→
Chloride intracellular channels modulate acute ethanol behaviors in Drosophila, Caenorhabditis elegans and mice.	Bhandari P et al.	—	2012	→
Complex control of GABA(A) receptor subunit mRNA expression: variation, covariation, and genetic regulation.	Mulligan MK et al.	—	2012	→
Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids.	Bryant CD et al.	—	2012	→
Forward genetic approaches to understanding complex behaviors.	Tarantino LM et al.	—	2012	→
Generating embryonic stem cells from the inbred mouse strain DBA/2J, a model of glaucoma and other complex diseases.	Reinholdt LG et al.	—	2012	→
Genetic and molecular network analysis of behavior.	Williams RW et al.	—	2012	→
Genetic control of a central pattern generator: rhythmic oromotor movement in mice is controlled by a major locus near Atp1a2.	Boughter JD et al.	—	2012	→
Genetic, morphometric, and behavioral factors linked to the midsagittal area of the corpus callosum.	Newbury AJ et al.	—	2012	→
Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains.	Parsons MJ et al.	—	2012	→
Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line.	Bryant CD et al.	—	2012	→
Systems genetic analysis of the effects of iron deficiency in mouse brain.	Jellen LC et al.	—	2012	→
Systems genetics of metabolism: the use of the BXD murine reference panel for multiscalar integration of traits.	Andreux PA et al.	—	2012	→
Systems genetics of the lateral septal nucleus in mouse: heritability, genetic control, and covariation with behavioral and morphological traits.	Talishinsky A et al.	—	2012	→
Anxiety and fear in a cross of C57BL/6J and DBA/2J mice: mapping overlapping and independent QTL for related traits.	Sokoloff G et al.	—	2011	→
Fetal alcohol spectrum disorders: gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes.	Reynolds JN et al.	—	2011	→
Genetic analysis in the Collaborative Cross breeding population.	Philip VM et al.	—	2011	→
Genetic analysis of the neurosteroid deoxycorticosterone and its relation to alcohol phenotypes: identification of QTLs and downstream gene regulation.	Porcu P et al.	—	2011	→
Genetic influences on exercise-induced adult hippocampal neurogenesis across 12 divergent mouse strains.	Clark PJ et al.	—	2011	→
Genetic regulation of Nrxn1 [corrected] expression: an integrative cross-species analysis of schizophrenia candidate genes.	Mozhui K et al.	—	2011	→
Genotype-dependent effects of adolescent nicotine exposure on dopamine functional dynamics in the nucleus accumbens shell in male and female mice: a potential mechanism underlying the gateway effect of nicotine.	Dickson PE et al.	—	2011	→
Novel candidate genes associated with hippocampal oscillations.	Jansen R et al.	—	2011	→
Reversed light-dark cycle and cage enrichment effects on ethanol-induced deficits in motor coordination assessed in inbred mouse strains with a compact battery of refined tests.	Munn E et al.	—	2011	→
The clinical implications of mouse models of enhanced anxiety.	Sartori SB et al.	—	2011	→
The genetic basis of adrenal gland weight and structure in BXD recombinant inbred mice.	Di Curzio DL et al.	—	2011	→
Appetitive operant conditioning in mice: heritability and dissociability of training stages.	Malkki HA et al.	—	2010	→
A transposon in Comt generates mRNA variants and causes widespread expression and behavioral differences among mice.	Li Z et al.	—	2010	→
Identifying genetic loci and spleen gene coexpression networks underlying immunophenotypes in BXD recombinant inbred mice.	Lynch RM et al.	—	2010	→