title: Striatal expression of Homer1a is affected by genotype but not dystonic phenotype of tottering mice: a model of spontaneously occurring motor disturbances.
abstract: Tottering (tg) mice carry a missense mutation in the gene coding for P/Q-type voltage-dependent Ca(2+) channels (VDCCs). Aberrant functioning of P/Q-type VDCCs results in molecular alterations in Ca(2+) currents and in glutamate and dopamine systems. As a consequence, tottering mice exhibit mild ataxia, spontaneous epilepsy, and paroxysmal dyskinesia. In this study, we evaluated whether the tottering mice genotype (homozygous vs. heterozygous) and abnormal movement phenotype (mice exhibiting paroxysmal dyskinesia vs. mice not exhibiting dyskinesia) may affect the expression of Homer1a. Homer1a is a gene whose expression is modulated by glutamate, dopamine and Ca(2+) concentrations. Over-expression of Homer1a has been described in epilepsy and motor dysfunctions. Thereby, changes in Homer1a expression could take place in tottering mice. Studying the expression profile of this gene may shed light on the molecular events occurring in tottering mice. Moreover, tottering mice may represent a valuable animal model for investigating Homer1a involvement in motor disorders. Homer1a expression was decreased in all striatal subregions, with the exclusion of the dorsolateral caudate-putamen, in heterozygous mice compared to wild-type and homozygous mice. Gene expression was decreased in the core of the accumbens in mice exhibiting paroxysmal dyskinesia compared to wild-type mice and to mice not exhibiting dyskinesia. These results demonstrate that the tottering mouse genotype may affect striatal expression of Homer1a, possibly as a result of imbalance between Ca(2+) channels subtypes or Ca(2+)-related molecules in heterozygous vs. homozygous mice.
authors: Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine Federico II, Edificio 18, Via Pansini 5, 80131 Naples, Italy.
authors: Felice
authors: F
authors: Iasevoli
authors: Maria
authors: M
authors: Cicale
authors: Louise C
authors: LC
authors: Abbott
authors: Andrea
authors: A
authors: de Bartolomeis
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D020820:Dyskinesias / Q000235:genetics*; D005838:Genotype; D000072233:Homer Scaffolding Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009069:Movement Disorders / Q000235:genetics*; D009714:Nucleus Accumbens / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015220:Calcium Channels; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D012333:RNA, Messenger