Open-Field Behavior in Mice: Evidence for a Major Gene Effect Mediated by the Visual System

DeFries, John C.; Hegmann, Joseph P.; Weir, Morton W.

doi:10.1126/science.154.3756.1577

Cited by 158 publications

(63 citation statements)

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“…The data suggest that the mutational spectrum underlying quantitative variation in behavior may be constrained to forms that alter gene expression, rather than abolishing it (as is the case with a Mendelian recessive), or altering the structure of a protein to produce a new effect (similar to a Mendelian dominant). However, I should caution you here that this conclusion is tentative, and that one case is known of a recessive mutation having a small effect on behavior, namely a tyrosinase mutant (c) effect on open-field activity and defecation in mice (DeFries, 1969;DeFries et al, 1966;Henry and Schlesinger, 1967;Wahlsten, 2001).…”

Section: Resultsmentioning

confidence: 98%

“…It shows how genotyping extremes can give rise to false negatives and underestimate of the number of QTL that influence a trait. For example, failure to detect the well known effect of the c locus (tyrosinase) on chromosome 7 on openfield activity in mice (DeFries, 1969;DeFries et al, 1966;Henry and Schlesinger, 1967;Wahlsten, 2001) is probably due to genotyping extreme phenotypes only (Flint et al, 1995;Turri et al, 2001b).…”

Section: Detection Of Small Genetic Effectsmentioning

confidence: 99%

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Analysis of quantitative trait loci that influence animal behavior

2002

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Behavioral differences between inbred strains of mice and rats have a genetic basis that can now be dissected using quantitative trait locus (QTL) analysis. Over the last 10 years, a large number of genetic loci that influence behavior have been mapped. In this article I review what that information has revealed about the genetic architecture of behavior. I show that most behaviors are influenced by QTL of small effect, each contributing to less than 10% of the variance of a behavioral trait. The small effect of each QTL on behavioral variation suggests that the mutational spectrum is different from that which results in Mendelian disorders. Regions of DNA should be appropriately prioritized to find the molecular variants, for instance by looking at sequences that control the level of gene expression rather than variants in coding regions. While the number of allelic loci that can contribute to a trait is large, this is not necessarily the case: the analysis of selected strains shows that a remarkably small number of QTL can explain the bulk of the genetic variation in behavior. I conclude by arguing that genetic mapping has more to offer than a starting point for positional cloning projects. With advances in multivariate analyses, mapping can also test hypotheses about the psychological processes that give rise to behavioral variation.

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Section: Resultsmentioning

confidence: 98%

Section: Detection Of Small Genetic Effectsmentioning

confidence: 99%

Analysis of quantitative trait loci that influence animal behavior

2002

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“…Our results provide a multitest extension of early work, which used an F5 generation from the progenitor strains of our current F2 mice. DeFries et al (1966) found that large open-field activity differences between albino and pigmented mice disappeared when testing was done under red light. They concluded that there is a major gene effect on openfield activity mediated by the visual system and that albino mice are more photophobic than pigmented mice under conditions of bright illumination.…”

Section: Profiles Of Qtl Actionmentioning

confidence: 98%

QTL Analysis of Multiple Behavioral Measures of Anxiety in Mice

et al. 2004

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In a test battery consisting of an open-field arena, a light-dark box, a mirror-chamber box, an elevated plus maze, and an elevated square maze, 1,671 mice were tested, generating over 100 putative measures of anxiety in rodents. Quantitative trait loci (QTL) analysis was carried out on all measures, plus composite measures and phenotypic factor scores. Significant LOD scores were found for QTL on 17 chromosomes, with large and consistent QTL behavioral effects on chromosomes 1, 4, 7, 8, 14, 15, l8, and X. QTL on chromosomes 4 and 8 largely influence locomotor activity in both home cages and novel environments, whereas QTL on chromosomes 1, 15, and 18 influence anxiety-related behaviors. Five genetically separable, cross-test dimensions of anxiety could be identified: (i) the suppression of locomotor activity in low to moderately anxiogenic regions of the tests; (ii) a shift toward proportionally less time and activity spent in high-anxiogenic test areas; (iii) the suppression of rearing behavior; (iv) increased latency to enter novel areas; (v) increased autonomic responses, as assessed by defecation and urination. Patterns of QTL influence on cross-test composite scores were distinctive. For example, the QTL on chromosome 1 strongly influenced safe-area locomotor activity (LOD = 35) and autonomic responses (LOD = 16), whereas the QTL on chromosome 15 influenced the proportion of activity in high-anxiogenic areas (LOD = 16), latency to enter novel areas (LOD = 36) and rearing behavior (LOD = 57). Phenotypic factor analysis identified factors heavily loaded on single tests, rather than cross-test factors. The use of factor analysis or within-test principal components for data reduction before genetic analysis was less satisfactory than using genetic dissection methods on the original measures and logically derived composites.

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“…) C57BL/6J mice (a pigmented strain) have higher activity and lower defecation scores than BALB/cJ mice (albino) when tested in the open field under conditions of moderately bright illumination (approximately 40 ft-c). In segregating F2, F3, and F4 generations, pigmented animals have also been found to have relatively higher activity and lower defecation scores than albinos, indicating that approximately 20% of the difference between the original inbred strains in both open-field activity and defecation was due to a single-gene difference at the albino locus (DeFries et al, 1966). These differences persisted when animals of an F5 generation were tested under white light, but largely disappeared when tested under red light; therefore, it was suggested that albino mice are more photophobic than pigmented animals.…”

Section: In Mice: Effect Of Testmentioning

confidence: 99%

Open-field behavior in mice: Effect of test illumination

1967

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In mice: Effect of testThe open-field behavior of two inbred strains of mice (BALBjc! and C57BLj6!) C57BL/6J mice (a pigmented strain) have higher activity and lower defecation scores than BALB/cJ mice (albino) when tested in the open field under conditions of moderately bright illumination (approximately 40 ft-c). In segregating F2, F3, and F4 generations, pigmented animals have also been found to have relatively higher activity and lower defecation scores than albinos, indicating that approximately 20% of the difference between the original inbred strains in both open-field activity and defecation was due to a single-gene difference at the albino locus (DeFries et al, 1966). These differences persisted when animals of an F5 generation were tested under white light, but largely disappeared when tested under red light; therefore, it was suggested that albino mice are more photophobic than pigmented animals.If differences in open-field behavior are due in part to a visually mediated fear reaction which is a function of illumination, then members of both inbred strains should manifest increased "emotionality" (higher defecation and lower activity) as level of test illumination is increased. However, if albinos are more photophobic than pigmented animals, members of the BALB/cJ strain should be more affected than those of the C57BL/6J strain by changes in test illumination, at least at the lower levels. In order to investigate these possibilities, the open-field behavior of these two inbred strains of mice was observed under five levels of illumination (0 to 480 ft-c) in approximately equal log steps. MethodMembers of two inbred strains of mice (BALB/cJ and C57BL/6J) were mated within strains at 70± 10 days of age and the resulting inbred offspring were tested at 40± 2 days of age in a square (24 x 24 x 8 in.) open field. The floor and sides of the field were of white, painted Plexiglas. Two sets of five light sources were beamed through holes and red

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Open-Field Behavior in Mice: Evidence for a Major Gene Effect Mediated by the Visual System

Cited by 158 publications

References 3 publications

Analysis of quantitative trait loci that influence animal behavior

Analysis of quantitative trait loci that influence animal behavior

QTL Analysis of Multiple Behavioral Measures of Anxiety in Mice

Open-field behavior in mice: Effect of test illumination

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