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Review
. 1994 Jun 17;264(5166):1724-33.
doi: 10.1126/science.8209253.

Forward and reverse genetic approaches to behavior in the mouse

Affiliations
Review

Forward and reverse genetic approaches to behavior in the mouse

J S Takahashi et al. Science. .

Abstract

Modern molecular genetic and genomic approaches are revolutionizing the study of behavior in the mouse. "Reverse genetics" (from gene to phenotype) with targeted gene transfer provides a powerful tool to dissect behavior and has been used successfully to study the effects of null mutations in genes implicated in the regulation of long-term potentiation and spatial learning in mice. In addition, "forward genetics" (from phenotype to gene) with high-efficiency mutagenesis in the mouse can uncover unknown genes and has been used to isolate a behavioral mutant of the circadian system. With the recent availability of high-density genetic maps and physical mapping resources, positional cloning of virtually any mutation is now feasible in the mouse. Together, these approaches permit a molecular analysis of both known and previously unknown genes regulating behavior.

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Figures

Fig. 1
Fig. 1
Mutagenesis screen. A behavioral test can be used to detect mutations in either first-or third-generation offspring of N-ethyi-N-nitrosourea (ENU)-treated males. (A) Genetic screen for dominant or semi-dominant mutations in first-generation (G1) offspring. Male mice were injected intraperitoneally with ENU to intervene at the stage of spermatogonia and enter a period of sterility. Upon recovery of fertility (12 to 16 weeks after treatment), they were bred with multiple females to produce G1 progeny that were heterozygous for any ENU-induced mutation (indicated by an asterisk). (B) Genetic screen for recessive mutations in third-generation (G3) offspring. In this scheme, G1 male progeny are bred with wild-type females to produce second-generation (G2) progeny. The G2 female progeny are then bred with their G1 father to produce G3 progeny. Compared to intercrossing G2 females and males, backcrossing G2 females to the G1 father doubles the likelihood of producing G3 progeny that are homozygous for a mutation.
Fig. 2
Fig. 2
Locomotor activity records of Clock mutant mice. The wheel-running activity records of three (BALB/cJ x C57BL/6J)F2 offspring are shown. All animals were kept on a light-dark cycle of 12 hours (LD 12:12) for the first 7 days illustrated, then transferred to constant darkness (DO) on the day indicated (line on the right); they later received a 6-hour light pulse on the day indicated (arrow). (A) Activity record of a wild-type F2 mouse. In DO, this animal’s activity rhythm had a period of 23.1 hours. (B) Activity record of a heterozygous Clock/+ F2 mouse. In DO, this animal’s activity rhythm had a period of 24.9 hours. (C) Activity record of a homozygous Clock/Clock F2 mouse. This individual had a complete loss of circadian rhythmicity upon transfer to DO, with a rhythm of 28.4 hours transiently expressed after the light pulse.

Comment in

  • Software availability.
    Goodman N, Lander ES, Oberai-Soltz R. Goodman N, et al. Science. 1995 Jan 6;267(5194):17. doi: 10.1126/science.7809601. Science. 1995. PMID: 7809601 No abstract available.

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