Abstract
The morphogenesis of the brain and the differentiation of the neural structures are highly complex processes. A series of temporally and spatially regulated morphogenetic events gives rise to smaller areas that are phylogenetically, functionally and often morphogenetically different1,2. Candidate genes for positional information and differentiation during morphogenesis have been isolated2–5. Both in vivo inactivation in mice6–8 and impairment in human diseases5,9 revealed, that they are required in regional specification and/or correct cell-type induction. We have previously cloned and characterized the murine Otx1 gene3,10, which is related to orthodentide (otd), a homeobox-containing gene required for Drosophila head development11,12. Expression data during murine embryogenesis3,10 and postnatal brain development13 support the idea that Otx1 could be required for correct brain and sense organs development. To decipher its role in vivo we produced null mice by replacing Otd1 with the lacZ gene. Otx1−/− mice showed spontaneous epileptic behaviour and multiple abnormalities affecting mainly the telencephalic temporal and perirhinal areas, the hippocampus, the mesencephalon and the cerebellum, as well as the acoustic and visual sense organs. Our findings indicate that the Otx1 gene product is required for proper brain functions.
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Acampora, D., Mazan, S., Avantaggiato, V. et al. Epilepsy and brain abnormalities in mice lacking the Otx1 gene. Nat Genet 14, 218–222 (1996). https://doi.org/10.1038/ng1096-218
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DOI: https://doi.org/10.1038/ng1096-218