D.B. and A.T. contributed equally to this work.
Inactivation of the gene for the nuclear receptor tailless in the brain preserving its function in the eye
Article first published online: 17 OCT 2007
European Journal of Neuroscience
Volume 26, Issue 8, pages 2222–2227, October 2007
How to Cite
Belz, T., Liu, H.-K., Bock, D., Takacs, A., Vogt, M., Wintermantel, T., Brandwein, C., Gass, P., Greiner, E. and Schütz, G. (2007), Inactivation of the gene for the nuclear receptor tailless in the brain preserving its function in the eye. European Journal of Neuroscience, 26: 2222–2227. doi: 10.1111/j.1460-9568.2007.05841.x
- Issue published online: 17 OCT 2007
- Article first published online: 17 OCT 2007
- Received 16 March 2007,revised 20 August 2007,accepted 21 August 2007
- conditional mutant;
- learning and memory;
During embryogenesis, tailless, an orphan member of the nuclear receptor family, is expressed in the germinal zones of the brain and the developing retina, and is involved in regulating the cell cycle of progenitor cells. Consequently, a deletion of the tailless gene leads to decreased cell number with associated anatomical defects in the limbic system, the cortex and the eye. These structural abnormalities are associated with blindness, increased aggressiveness, poor performance in learning paradigms and reduced anxiousness. In order to assess the contribution of blindness to the behavioural changes, we established tailless mutant mice with intact visual abilities. We generated a mouse line in which the second exon of the tailless gene is flanked by loxP sites and crossed these animals with a transgenic line expressing the Cre recombinase in the neurogenic area of the developing brain, but not in the eye. The resulting animals have anatomically indistinguishable brains compared with tailless germline mutants, but are not blind. They are less anxious and much more aggressive than controls, like tailless germline mutants. In contrast to germline mutants, the conditional mutants are not impaired in fear conditioning. Furthermore, they show good performance in the Morris water-maze despite severely reduced hippocampal structures. Thus, the pathological aggressiveness and reduced anxiety found in tailless germline mutants are due to malformations caused by inactivation of the tailless gene in the brain, but the poor performance of tailless null mice in learning and memory paradigms is dependent on the associated blindness.