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

First Author  Borgkvist A Year  2006
Journal  Mol Cell Neurosci Volume  31
Issue  2 Pages  293-302
PubMed ID  16256364 Mgi Jnum  J:106889
Mgi Id  MGI:3619716 Doi  10.1016/j.mcn.2005.09.018
Citation  Borgkvist A, et al. (2006) Altered dopaminergic innervation and amphetamine response in adult Otx2 conditional mutant mice. Mol Cell Neurosci 31(2):293-302
abstractText  Here, we have investigated the neurological consequences of restricted inactivation of Otx2 in adult En1(cre/+); Otx2(flox/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/+); Otx2(flox/flox) mutant mouse model represents a genetic tool for investigating molecular and behavioural consequences of developmental neuronal dysfunction in the DAergic system.
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