Altered dopaminergic innervation and amphetamine response in adult Otx2 conditional mutant mice

Anders Borgkvist, Eduardo Puelles, Manolo Carta, Dario Acampora, Siew Lan Ang, Wolfgang Wurst, Michel Goiny, Gilberto Fisone, Antonio Simeone, Alessandro Usiello

Research output: Contribution to journalArticlepeer-review

Abstract

Here, we have investigated the neurological consequences of restricted inactivation of Otx2 in adult En1cre/+; Otx2flox/flox mice. In agreement with the crucial role of Otx2 in midbrain patterning, the mutants had a substantial reduction in tyrosine hydroxylase containing neurons. Although the reduction in the number of DAergic neurons was comparable between the SNc and the VTA, we found an unexpected selectivity in the deinnervation of the terminal fields affecting preferentially the ventral striatum and the olfactory tubercle. Interestingly, the mutants showed no abnormalities in exploratory activity or motor coordination. However, the absence of normal DA tone generated significant alterations in DA D1-receptor signalling as indicated by increased mutant striatal levels of phosphorylated DARPP-32 and by an altered motor response to amphetamine. Therefore, we suggest that the En1 cre/+; Otx2flox/flox mutant mouse model represents a genetic tool for investigating molecular and behavioural consequences of developmental neuronal dysfunction in the DAergic system.

Original languageEnglish
Pages (from-to)293-302
Number of pages10
JournalMolecular and Cellular Neuroscience
Volume31
Issue number2
DOIs
Publication statusPublished - Feb 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

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