High-throughput behavioral phenotyping in the expanded panel of BXD recombinant inbred strains - PubMed (original) (raw)

. 2010 Mar 1;9(2):129-59.

doi: 10.1111/j.1601-183X.2009.00540.x. Epub 2009 Sep 22.

S Duvvuru, B Gomero, T A Ansah, C D Blaha, M N Cook, K M Hamre, W R Lariviere, D B Matthews, G Mittleman, D Goldowitz, E J Chesler

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Free PMC article

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

V M Philip et al. Genes Brain Behav. 2010.

Free PMC article

Abstract

Genetic reference populations, particularly the BXD recombinant inbred (BXD RI) strains derived from C57BL/6J and DBA/2J mice, are a valuable resource for the discovery of the bio-molecular substrates and genetic drivers responsible for trait variation and covariation. This approach can be profitably applied in the analysis of susceptibility and mechanisms of drug and alcohol use disorders for which many predisposing behaviors may predict the occurrence and manifestation of increased preference for these substances. Many of these traits are modeled by common mouse behavioral assays, facilitating the detection of patterns and sources of genetic coregulation of predisposing phenotypes and substance consumption. Members of the Tennessee Mouse Genome Consortium (TMGC) have obtained phenotype data from over 250 measures related to multiple behavioral assays across several batteries: response to, and withdrawal from cocaine, 3,4-methylenedioxymethamphetamine; "ecstasy" (MDMA), morphine and alcohol; novelty seeking; behavioral despair and related neurological phenomena; pain sensitivity; stress sensitivity; anxiety; hyperactivity and sleep/wake cycles. All traits have been measured in both sexes in approximately 70 strains of the recently expanded panel of BXD RI strains. Sex differences and heritability estimates were obtained for each trait, and a comparison of early (N = 32) and recent (N = 37) BXD RI lines was performed. Primary data are publicly available for heritability, sex difference and genetic analyses using the MouseTrack database, and are also available in GeneNetwork.org for quantitative trait locus (QTL) detection and genetic analysis of gene expression. Together with the results of related studies, these data form a public resource for integrative systems genetic analysis of neurobehavioral traits.

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Figures

Figure 1

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.

Figure 3

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.

Figure 2

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).

Figure 2

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).

Figure 4

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.

Figure 5

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 r_Memphis,UTHSC = 0.556,r_Memphis,Demarest = 0.781 and _r_Demarest,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.

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