title: Phenotypic disruption to orofacial movement topography in conditional mutants with generalized CamKIIa/Cre D1Tox versus striatal-specific DARPP-32/Cre D1Tox ablation of D1 dopamine receptor-expressing cells.
abstract: Orofacial movements were quantified in (a) DARPP-32/Cre D1Tox mutants, having progressive loss of D1 dopamine receptor expressing striatal medium spiny neurons and (b) CamKIIa/Cre D1Tox mutants, having progressive, generalized loss of forebrain D1 receptor expressing cells. Horizontal jaw movements and tongue protrusions were reduced in DARPP-32/Cre but not in CamKIIa/Cre mutants; head and vibrissae movements were increased in DARPP-32/Cre but decreased in CamKIIa/Cre mutants. In drug challenge studies, tongue protrusions were increased in CamKIIa/Cre mutants following vehicle, suggesting a stress-related phenotype. These findings indicate that mice with progressive loss of striatal-specific D1 receptor expressing cells have an orofacial phenotype that may be modulated by the loss of extrastriatal D1 receptor expressing cells. As progressive loss of D1 dopamine receptor-expressing cells is a hallmark feature of Huntington's disease (HD), these findings may inform the functional role of loss of this cell population in the overall pathobiology of HD.
authors.affiliation: Advanced Research Institute for the Sciences and Humanities, Nihon University, Tokyo 102, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tomiyama
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
authors.forename: Anthony
authors.initials: A
authors.lastname: Kinsella
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Ehrlich
authors.forename: Günter
authors.initials: G
authors.lastname: Schütz
authors.forename: Noriaki
authors.initials: N
authors.lastname: Koshikawa
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.forename: John L
authors.initials: JL
authors.lastname: Waddington
authors.forename: John
authors.initials: J
authors.lastname: Drago
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics*; D003342:Corpus Striatum / Q000473:pathology*; D004167:Diphtheria Toxin / Q000235:genetics*; D018491:Dopamine Agonists / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005145:Face / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009068:Movement / Q000187:drug effects; D009069:Movement Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics*; D010641:Phenotype; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004167:Diphtheria Toxin; D018491:Dopamine Agonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D010446:Peptide Fragments; C497929:Ppp1r1b protein, mouse; D017447:Receptors, Dopamine D1; C029795:diphtheria toxin fragment A; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C080703:SK&F 83959; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517671:Camk2a protein, mouse