title: Decreased gene expression of calretinin and ryanodine receptor type 1 in tottering mice.
abstract: Tottering mice are a spontaneously occurring animal model of human absence epilepsy. They carry a mutation in the P/Q-type calcium channel alpha1A subunit gene which is highly expressed by cerebellar Purkinje cells. In this study, we investigated the role of calretinin and ryanodine receptor type 1 (RyR1) gene expression in the cerebellum of tottering mice. Cerebellar tissue specimens from four experimental groups were processed for in situ hybridization histochemistry (ISHH): (1) wild-type (+/+); (2) heterozygous (tg/+) and two homozygous groups; either (3) without occurrence of an episode of paroxysmal dyskinesia (tg/tg-N); or (4) after an episode of paroxysmal dyskinesia (tg/tg-P) that lasted about 45 min on average. Quantitative analysis showed a statistically significant decrease (p = 0.0001, ANOVA) of calretinin gene expression at the level of the simple lobule of the cerebellum in both homozygous groups compared to the wild-type and heterozygous groups. RyR1 was decreased in the flocculus of the cerebellum in both the tg/tg-N and tg/tg-P groups compared to wild type (p = 0.0174, ANOVA). These results suggest that calretinin gene expression, as well as other genes involved in regulation of calcium homeostasis, such as RyR1, may play a role in the biochemical functional alterations present in tottering mice.
authors.affiliation: Department of Neuroscience and Behavioral Sciences, Unit of Molecular Psychiatry, Section of Psychiatry, University School of Medicine Federico II, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cicale
authors.forename: A
authors.initials: A
authors.lastname: Ambesi-Impiombato
authors.forename: V
authors.initials: V
authors.lastname: Cimini
authors.forename: G
authors.initials: G
authors.lastname: Fiore
authors.forename: G
authors.initials: G
authors.lastname: Muscettola
authors.forename: L C
authors.initials: LC
authors.lastname: Abbott
authors.forename: A
authors.initials: A
authors.lastname: de Bartolomeis
mesh_terms: D000818:Animals; D064032:Calbindin 2; D002118:Calcium / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000172:deficiency / Q000235:genetics; D020013:Calcium Signaling / Q000235:genetics*; D002531:Cerebellum / Q000378:metabolism* / Q000503:physiopathology; D002819:Chorea / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D004832:Epilepsy, Absence / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009154:Mutation / Q000235:genetics; D011689:Purkinje Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism*
chemical_list: C576764:CALB2 protein, human; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D020865:Calcium Channels, P-Type; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D064030:S100 Calcium Binding Protein G; D002118:Calcium