Staggerer, a New Mutation in the Mouse Affecting the Cerebellum

Sidman, Richard L.; Lane, Priscilla W.; Dickie, Margaret M.

doi:10.1126/science.137.3530.610

Cited by 358 publications

(141 citation statements)

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“…Mice with staggerer were found to carry a deletion within the ROR␣ gene that blocks Purkinje cells differentiation, resulting in congenital ataxia and cerebellar hypoplasia (Sidman et al, 1962;Dussault et al, 1998), and ROR␣ knockout mice show phenotypes similar to those seen with staggerer mice (Dussault et al, 1998;Steinmayr et al, 1998;Gold et al, 2003). Given these phenotypes, we next systematically analyzed the ROR␣ expression pattern in the cerebellum during different developmental stages.…”

Section: The Expression Patterns Of Err␥ Ror␣ and Er␤ In The Develomentioning

confidence: 99%

The expression pattern of nuclear receptors during cerebellar development

Qin

Suh

Kim

et al. 2007

Developmental Dynamics

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Section: The Expression Patterns Of Err␥ Ror␣ and Er␤ In The Develomentioning

confidence: 99%

The expression pattern of nuclear receptors during cerebellar development

Qin

Suh

Kim

et al. 2007

Developmental Dynamics

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“…This autosomal recessive mutation results in a lack of granule cells (Sidman et al, 1962), reduced numbers of Purkinje cells (Herrup and Mullen, 1979), and malformation of the residual Purkinje cells (Landis and Sidman, 1978;Sotelo. 1975).…”

Section: Staggerer (Sg)mentioning

confidence: 99%

“…We also examined the dopamine content of these striatal districts in 2 other mutant mouse types exhibiting movement disorders as a result of autosomal recessive mutations expressed in the cerebellum. One of these, the staggerer mutant (sg), has in common with weaver a granule cell-deficient cerebellum (Sidman et al, 1962). The other, Purkinje cell degeneration (pcd), has in common an ataxia, but loses the Purkinje cells of the cerebellum 3319 3320 Graybiel Vol.…”

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confidence: 99%

Expression of the weaver gene in dopamine-containing neural systems is dose-dependent and affects both striatal and nonstriatal regions

Roffler-Tarlov¹,

Graybiel²

1986

J. Neurosci.

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In an earlier report we presented evidence pointing to a differential effect of the mutant gene weaver on the dopamine-containing fiber systems innervating the striatum. In mice homozygous for the weaver mutation, there is a severe loss of dopamine in the caudoputamen, the main target of the nigrostriatal system. By contrast, dopamine is entirely conserved in the nucleus accumbens, a target of the mesolimbic system, and is moderately affected in the olfactory tubercle. The present study shows that these defects in dopamine are gene dose-dependent, that they are established by the end of the first month of life, and that the losses are permanent and not progressive. As in homozygous weavers, the greatest defects in striatal dopamine in heterozygous weavers occur in the dorsolateral caudoputamen and the lateral olfactory tubercle.The abnormalities in the striatal dopamine content of weaver mice are not accompanied by abnormalities in the turnover of dopamine, judging from measurements of the dopamine metabolite dihydroxyphenylacetic acid. Norepinephrine content is also normal in each striatal region. No deficits in striatal dopamine occur in mice homozygous for the mutant genes staggerer and Purkinje cell degeneration, which, like the weaver mutation, result in ataxia and cerebellar pathology.A survey of nonstriatal regions in the weaver mice showed that the effects of the weaver gene on the dopamine-containing innervation of the forebrain are not confined to striatal targets but also extend to the septum and the hypothalamus. By contrast, dopamine in the frontal cortex, the amygdala, the olfactory bulb, and the retina is entirely spared. The pattern and extent of loss of dopamine in the weaver forebrain is thus regionand system-specific. In confirmation of our initial findings, a ca. 30% depletion of dopamine occurs in the weaver midbrain, the region containing the cell bodies of origin of the mesostriatal dopamine systems. A comparison of histofluorescent sections through weaver and control midbrains revealed a reduction of catecholamine-containing neurons in the pars compacta of the weaver animals.These results point to a subpopulation of dopamine-containing neurons as primary targets of the weaver gene or as being closely associated with such primary targets. As a gene-dose effect has also been shown for the cerebellar granule cell loss in the weaver, the mutant gene must have at least 2 cellular Received Jan. 7, 1986; revised Apr. 30, 1986; accepted May 5, 1986. This work was supported by National Institutes of Health targets. We suggest that the cerebellar and mesostriatal pathologies may be linked by a common molecular mechanism.Two defects, one obvious and the other well hidden, are known to be present in the brains of mice that carry the autosomal recessive gene weaver. This mutation results in an atrophy of the cerebellum that is so severe in homozygous weavers that it can be detected after a glance at the intact brain. As was first reported by Sidman et al. in 1965, this macroscopic defect reflects an...

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“…Homozygous staggerer mutant mouse (Rora sg/sg ), as well as transgenic mice in which the Rora gene has been disrupted (Rora -/-), display a severe ataxic phenotype associated with a strong cerebellar hypoplasia, a consequence of the degeneration of a large majority of Purkinje cells during development and the consequent absence of virtually all granule cells (1,2). Interestingly, the few surviving Purkinje cells display immature shapes and abnormal differentiation.…”

Section: Introductionmentioning

confidence: 99%

Rorα, a pivotal nuclear receptor for Purkinje neuron survival and differentiation: From development to ageing

et al. 2006

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Abstract:RORα (Retinoid-related Orphan Receptor) is a transcription factor belonging to the superfamily of nuclear receptors. The spontaneous staggerer (sg) mutation, which consists of a deletion in the Rora ge ne, has been shown to cause the loss of function of the RORα protein. The total loss of RORα expression leads to cerebellar developmental defects, particularly to a dramatic decreased survival of Purkinje cells and an early block in the differentiation process. This review focuses on recent studies which position RORα as a pivotal factor controlling Purkinje cell survival and differentiation, from development to ageing.

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Staggerer, a New Mutation in the Mouse Affecting the Cerebellum

Cited by 358 publications

References 4 publications

The expression pattern of nuclear receptors during cerebellar development

The expression pattern of nuclear receptors during cerebellar development

Expression of the weaver gene in dopamine-containing neural systems is dose-dependent and affects both striatal and nonstriatal regions

Rorα, a pivotal nuclear receptor for Purkinje neuron survival and differentiation: From development to ageing

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