TY - JOUR
T1 - Altered dopaminergic innervation and amphetamine response in adult Otx2 conditional mutant mice
AU - Borgkvist, Anders
AU - Puelles, Eduardo
AU - Carta, Manolo
AU - Acampora, Dario
AU - Ang, Siew Lan
AU - Wurst, Wolfgang
AU - Goiny, Michel
AU - Fisone, Gilberto
AU - Simeone, Antonio
AU - Usiello, Alessandro
N1 - Funding Information:
We thank Bernardini N., Clifford J.J., Bozzi Y. and Valente E.M. for helpful comments and discussions on the manuscript. We are also indebted to Papalia A. for excellent animal care. This work was supported by the MRC Programme N. G9900955, the Wellcome Trust Programme Grant N. 062642/Z/00, the Italian Association for Cancer Research (AIRC), the FIRB Neuroscienze PNR 2001–2003 (FIRB art.8) D.M. 199 and the Fondation Bettencourt-Schueller to A.S. The Eumorphia Programme QLRT-2001-00930 and the Bundesministerium für Bildung und Forschung NGFN-2 to WW; The Swedish Research Council grants 13482 and 14518 to G.F; The Wenner-Gren Foundations, Fondazione Agarini and Mariano Scippacercola to A.U.
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/32244432674
U2 - 10.1016/j.mcn.2005.09.018
DO - 10.1016/j.mcn.2005.09.018
M3 - Article
C2 - 16256364
AN - SCOPUS:32244432674
SN - 1044-7431
VL - 31
SP - 293
EP - 302
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 2
ER -