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|Title:||Motor and behavioral phenotype in conditional mutants with targeted ablation of cortical D1 dopamine receptor-expressing cells.|
|Authors:||Jiang, Luning;O'Leary, Claire;Kim, Hyun Ah;Parish, Clare L;Massalas, Jim;Waddington, John L;Ehrlich, Michelle E;Schütz, Günter;Gantois, Ilse;Lawrence, Andrew J;Drago, John|
|Affiliation:||Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia; St Vincent's Hospital, Melbourne, Victoria, Australia.|
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia; Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia; St Vincent's Hospital, Melbourne, Victoria, Australia. Electronic address: email@example.com.
|Citation:||Neurobiology of Disease 2015; 76(): 137-58|
|Abstract:||D1-dopamine receptors (Drd1a) are highly expressed in the deep layers of the cerebral cortex and the striatum. A number of human diseases such as Huntington disease and schizophrenia are known to have cortical pathology involving dopamine receptor expressing neurons. To illuminate their functional role, we exploited a Cre/Lox molecular paradigm to generate Emx-1(tox) MUT mice, a transgenic line in which cortical Drd1a-expressing pyramidal neurons were selectively ablated. Emx-1(tox) MUT mice displayed prominent forelimb dystonia, hyperkinesia, ataxia on rotarod testing, heightened anxiety-like behavior, and age-dependent abnormalities in a test of social interaction. The latter occurred in the context of normal working memory on testing in the Y-maze and for novel object recognition. Some motor and behavioral abnormalities in Emx-1(tox) MUT mice overlapped with those in CamKIIα(tox) MUT transgenic mice, a line in which both striatal and cortical Drd1a-expressing cells were ablated. Although Emx-1(tox) MUT mice had normal striatal anatomy, both Emx-1(tox) MUT and CamKIIα(tox) MUT mice displayed selective neuronal loss in cortical layers V and VI. This study shows that loss of cortical Drd1a-expressing cells is sufficient to produce deficits in multiple motor and behavioral domains, independent of striatal mechanisms. Primary cortical changes in the D1 dopamine receptor compartment are therefore likely to model a number of core clinical features in disorders such as Huntington disease and schizophrenia.|
|Internal ID Number:||25684539|
Targeted cell deletion
|Appears in Collections:||Journal articles|
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