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Defective limbic system in mice lacking the tailless gene

Nature volume 390, pages 515–517 (1997)Cite this article

Abstract

The gene tailless is a member of the superfamily of genes that encode transcription factors of the ligand-activated nuclear receptor type, and is expressed in the invertebrate and vertebrate brain1,2,3,4. In mice, its transcripts are restricted to the periventricular zone of the forebrain4, the site of origin of neurons and glia. Here we use homologous recombination to generate mice that lack a functional tailless protein. Homozygous mutant mice are viable at birth, indicating that tailless is not required for prenatal survival; however, adult mutant mice show a reduction in the size of rhinencephalic and limbic structures, including the olfactory, infrarhinal and entorhinal cortex, amygdala and dentate gyrus. Both male and female mice are more aggressive than usual and females lack normal maternal instincts. These animals therefore enable a molecular approach to be taken towards understanding the genetic architecture and morphogenesis of the forebrain.

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Figure 1: Targeted disruption of the tlx gene.
Figure 2: Growth of tailless mutant mice is retarded and they have smaller cerebral hemispheres.
Figure 3: Reduced size of hemispheres of tailless mutants is due to defective rhinencephalic structures.
Figure 4: Reduction of neuronal subpopulations in tlx mutant mice.
Figure 5: Developmental abnormalities in tlx mutant mice.

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Acknowledgements

We thank E. Grau, E. Schmid, S. Ridder, H. Glaser and A. Klewe-Nebenius for technical assistance; J. Blendy, H. Kaestner and M. Nichols for critically reading the manuscript; R. Lang and M. Stagliar-Bozicevic for help with behavioural analyses; W. Fleischer for help with photography; and M. Bock for secretarial assistance. This work was supported by the Deutsche Forschungsgemeinschaft, the European Community, BMBF (Forschungszentrum Jülich/Schering), Fonds der Chemischen Industrie, by the Swiss National Foundation for Scientific Research and the Human Science Frontier Programme (to H.P.L.).

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Authors and Affiliations

  1. Division of Molecular Biology of the Cell I, German Cancer Research Centre, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany

    A. P. Monaghan, D. Bock, P. Gass, A. Schwger & G. Schütz

  2. Institute of Anatomy, University of Zürich-Irchel, Zürich, 8057, Switzerland

    D. P. Wolfer & H.-P. Lipp

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  1. A. P. Monaghan
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  2. D. Bock
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  3. P. Gass
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  5. D. P. Wolfer
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  7. G. Schütz
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Correspondence to G. Schütz.

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Monaghan, A., Bock, D., Gass, P. et al. Defective limbic system in mice lacking the tailless gene. Nature 390, 515–517 (1997). https://doi.org/10.1038/37364

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