Decreased gene expression of calretinin and ryanodine receptor type 1 in tottering mice

• Published in: Brain research bulletin Vol. 59; no. 1; pp. 53 - 58
• Main Authors: CICALE, M, AMBESI-IMPIOMBATO, A, CIMINI, V, FIORE, G, MUSCETTOLA, G, ABBOTT, L. C, DE BARTOLOMEIS, A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 15.10.2002
• Subjects: Animals; Biological and medical sciences; Calbindin 2; Calcium - metabolism; Calcium Channels, P-Type - deficiency; Calcium Channels, P-Type - genetics; Calcium Signaling - genetics; Cerebellum - metabolism; Cerebellum - physiopathology; Chorea - genetics; Chorea - metabolism; Chorea - physiopathology; Disease Models, Animal; Down-Regulation - genetics; Epilepsy, Absence - genetics; Epilepsy, Absence - metabolism; Epilepsy, Absence - physiopathology; Female; Gene Expression Regulation - physiology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Homeostasis - genetics; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Neurologic Mutants; Mutation - genetics; Nervous system (semeiology, syndromes); Neurology; Purkinje Cells - metabolism; RNA, Messenger - metabolism; Ryanodine Receptor Calcium Release Channel - genetics; Ryanodine Receptor Calcium Release Channel - metabolism; S100 Calcium Binding Protein G - genetics; S100 Calcium Binding Protein G - metabolism; Cerebellum; Animal model; Nervous system diseases; Calcium; Calretinin; Epilepsy; Rodentia; Ryanodine receptor; Petit mal; mRNA; Gene expression; Cerebral disorder; Calcium binding proteins; Binding protein; Vertebrata; Mammalia; Mouse; In situ hybridization histochemistry; Central nervous system disease; Paroxysmal dyskinesia
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/s0361-9230(02)00841-9

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.