Multivariate Analysis of Temporal Descriptions of Open-field Behavior in Wild-derived Mouse Strains

Takahashi, Akiyoshi; Kato, Katsunori; Makino, Junshiro; Shiroishi, Toshihiko; Koide, Tsuyoshi

doi:10.1007/s10519-005-9038-3

Cited by 55 publications

(54 citation statements)

References 56 publications

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“…In the analyses of complex traits in wild-derived strains, we identified a marked diversity of phenotypes among strains [12,17,24,29]. The phenotypic diversity is believed to be a result of genetic diversity among wild-derived strains, as shown by several studies on genomic polymorphisms of these strains [17,18,20,23,27].…”

Section: Proposal Of a New Approach To Elucidate Complex Traitsmentioning

confidence: 95%

Genomic Mixing to Elucidate the Genetic System of Complex Traits

2012

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Abstract:Understanding the genetic basis of complex traits has become one of the major issues in genetics, but recent advances in this field are still faced with a difficulty, the so-called "missing heritability." It is speculated that missing heritability mainly stems from a large number of variants of small effect that are poorly detected by currently available methods. In order to overcome this problem, many recent genetic studies of complex traits have actively used outbred stocks of mice. However, most of the available outbred stocks have a limited amount of genetic variation, because many stocks originate from Swiss mouse colonies. We have repeatedly shown that wild-derived strains are a useful mouse resource since there is a large genetic diversity among these strains. Here, we give an overview of mouse resources produced by crossing different founder mice. Finally, we propose an advantage of new attempts to conduct selective breeding using heterogeneous stocks created by mixing genomes of wild-derived inbred strains of mice when studying complex traits.

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Section: Proposal Of a New Approach To Elucidate Complex Traitsmentioning

confidence: 95%

Genomic Mixing to Elucidate the Genetic System of Complex Traits

2012

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“…We bred several of these mutant lines for another generation and confirmed that the phenotypes were indeed heritable. PCA and factor analysis have been extensively used to study rodent behavior and have also been applied to QTL analysis for behavioral measures (30,(42)(43)(44). Use of multivariate analysis has led to the discovery of unique QTLs regulating latent behaviors that cannot be directly measured, such as fearfulness and anxiety (45,46).…”

Section: Discussionmentioning

confidence: 99%

Second-generation high-throughput forward genetic screen in mice to isolate subtle behavioral mutants

Kumar

Kim

Joseph

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Forward genetic screens have been highly successful in revealing roles of genes and pathways in complex biological events. Traditionally these screens have focused on isolating mutants with the greatest phenotypic deviance, with the hopes of discovering genes that are central to the biological event being investigated. Behavioral screens in mice typically use simple activity-based assays as endophenotypes for more complex emotional states of the animal. They generally set the selection threshold for a putative mutant at 3 SDs (z score of 3) from the average behavior of normal animals to minimize false-positive results. Behavioral screens using a high threshold for detection have generally had limited success, with high false-positive rates and subtle phenotypic differences that have made mapping and cloning difficult. In addition, targeted reverse genetic approaches have shown that when genes central to behaviors such as open field behavior, psychostimulant response, and learning and memory tasks are mutated, they produce subtle phenotypes that differ from wild-type animals by 1 to 2 SDs (z scores of 1 to 2). We have conducted a second-generation (G2) dominant Nethyl-N-nitrosourea (ENU) screen especially designed to detect subtle behavioral mutants for open field activity and psychostimulant response behaviors. We successfully detect mutant lines with only 1 to 2 SD shifts in mean response compared with wild-type control animals and present a robust statistical and methodological framework for conducting such forward genetic screens. Using this methodology we have screened 229 ENU mutant lines and have identified 15 heritable mutant lines. We conclude that for screens in mice that use activity-based endophenotypic measurements for complex behavioral states, this G2 screening approach yields better results.

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“…In order to study behavioral differences, a variety of behavioral analyses have been applied to the Mishima battery [10,14,22,25]. The results obtained in these studies are good examples of the usefulness of the Mishima battery.…”

Section: Behavioral Traits In Wild Strainsmentioning

confidence: 99%

A New Twist on Behavioral Genetics by Incorporating Wild-Derived Mouse Strains

Koide

Ikeda

Ogasawara³

et al. 2011

Exp. Anim.

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Abstract:Behavior has been proven to be extremely variable among human individuals. One of the most important factors for such variations of behavior is genetic diversity. A variety of mouse strains are reportedly suitable animal models for investigating the genetic basis of large individual differences in behavior. Laboratory strains have been shown to exhibit different behavioral traits due to variations in their genetic background. However, they show low-level genetic polymorphism because the original colony used for establishing the strains comprises a relatively small number of mice. Furthermore, because the laboratory strains were derived from fancy mice, they have lost the original behavioral phenotype of wild mice. Therefore, incorporation of inbred strains derived from wild mice of different mouse subspecies for behavioral studies is a marked advantage. In the long-term process of establishing a variety of wild-derived inbred strains from wild mice captured all over the world, a number of strains have been established. We previously identified a marked variety in behavioral traits using a Mishima battery. This review reports on the usefulness of wild-derived strains for genetic analyses of behavioral phenotypes in mice.

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Multivariate Analysis of Temporal Descriptions of Open-field Behavior in Wild-derived Mouse Strains

Cited by 55 publications

References 56 publications

Genomic Mixing to Elucidate the Genetic System of Complex Traits

Genomic Mixing to Elucidate the Genetic System of Complex Traits

Second-generation high-throughput forward genetic screen in mice to isolate subtle behavioral mutants

A New Twist on Behavioral Genetics by Incorporating Wild-Derived Mouse Strains

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