Cellular and Animal Models of Cerebellar Disorders: Staggerer Mouse
The staggerer mutant mouse carries a spontaneous mutation in the ligand-binding domain of the rora gene. RORα is expressed in many tissues and its loss leads to diverse abnormalities. In the cerebellum of staggerer mice, there is severe early degeneration of Purkinje cells and associated death of their afferent neurons (granule and olivary neurons). Thus staggerer mice have atrophic cerebella and associated severe ataxia. In contrast, although heterozygote staggerer mice develop apparently normally, there is premature Purkinje cell atrophy and death in adulthood. Given that recent links have been demonstrated between RORα and spinocerebellar ataxia and autism spectrum disorders, the staggerer mouse is a particularly interesting model for cerebellar pathologies.
KeywordsPurkinje Cell Neuroprotection Autism Spectrum Disorders Anti-Inflammatory Action Orphan Nuclear Receptor Spinocerebellar Ataxia
- Chen X, Heck N, Lohof AM, Rochefort C, Morel MP, Wehrlé R, Doulazmi M, Cannaya V, Avci HX, Mariani J, Rondi-Reig L, Vodjdani G, Sherrard RM, Sotelo C, Dusart I (2013) Mature Purkinje cells require the retinoic acid-related orphan receptor alpha (RORα) to maintain climbing fiber monoinnervation and other adult characteristics. J Neurosci 33(22):9546–9562CrossRefPubMedGoogle Scholar
- Fatemi SH, Aldinger KA, Ashwood P, Bauman ML, Blaha CD, Blatt GJ, Chauhan A, Chauhan V, Dager SR, Dickson PE, Estes AM, Goldowitz D, Heck DH, Kemper TL, King BH, Martin LA, Millen KJ, Mittleman G, Mosconi MW, Persico AM, Sweeney JA, Webb SJ, Welsh JP (2012) Consensus paper: pathological role of the cerebellum in Autism. Cerebellum 11:777–807CrossRefPubMedPubMedCentralGoogle Scholar
- Janmaat S, Akwa Y, Doulazmi M, Bakouche J, Gautheron V, Liere P, Eychenne B, Pianos A, Luiten P, Groothuis T, Baulieu EE, Mariani J, Sherrard RM, Frederic F (2011) Age-related Purkinje cell death is steroid dependent: RORalpha haplo-insufficiency impairs plasma and cerebellar steroids and Purkinje cell survival. Age 33:565–578CrossRefPubMedPubMedCentralGoogle Scholar
- Journiac N, Jolly S, Jarvis C, Gautheron V, Rogard M, Trembleau A, Blondeau JP, Mariani J, Vernet-der Garabedian B (2009) The nuclear receptor ROR(alpha) exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes. Proc Natl Acad Sci U S A 106:21365–21370CrossRefPubMedPubMedCentralGoogle Scholar