Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood disorders, autism and lissencephaly

Fatemi, S. Hossein

doi:10.1038/sj.mp.4000129

Cited by 136 publications

(84 citation statements)

References 65 publications

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“…Thus, it may be that heterozygous reeler mice are a better model of learning deficits that are also associated with many psychiatric disorders than of the prefrontal cognitive symptoms related more specifically to schizophrenia. This hypothesis is consistent with reports of associations between reelin and a wide range of psychiatric and neurodevelopmental disorders, including bipolar disorder, major depression, autism and lissencephaly (Fatemi, 2001;D'Arcangelo, 2006).…”

Section: Discussionsupporting

confidence: 79%

Assessment of cognitive function in the heterozygous reeler mouse

et al. 2006

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RATIONALE-The heterozygous reeler mouse has been proposed as a genetic mouse model of schizophrenia, based on several neuroanatomical and behavioral similarities between these mice and patients with schizophrenia. However, the effect of reelin haploinsufficiency on one of the cardinal symptoms of schizophrenia, the impairment of prefrontal cortex-dependent cognitive function, has yet to be determined.OBJECTIVE-Here, we investigated multiple aspects of cognitive function in heterozygous reeler mice that are known to be impaired in schizophrenic patients.METHODS-Heterozygous reeler mice were assessed for (1) cognitive flexibility in an instrumental reversal learning task; (2) impulsivity in an inhibitory control task; (3) attentional function in a threechoice serial reaction time task; and (4) working memory in a delayed matching-to-position task.RESULTS-No differences were found between heterozygous reeler mice and wild-type littermate controls in any prefrontal-related cognitive measures. However, heterozygous reeler mice showed deficits in the acquisition of two operant tasks, consistent with a role for reelin in certain forms of learning.CONCLUSIONS-These findings suggest that heterozygous reeler mice may not be an appropriate model for the core prefrontal-dependent cognitive deficits observed in schizophrenia, but may model more general learning deficits that are associated with many psychiatric disorders.

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Section: Discussionsupporting

confidence: 79%

Assessment of cognitive function in the heterozygous reeler mouse

et al. 2006

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“…More interestingly, several experimental paradigms and haploinsufficiency in Reln gene in mice also cause decreases in Reelin production with resultant cortical and behavioral abnormalities. 18,[39][40][41] In the heterozygous reeler mutation, there is a 50% reduction in Reelin protein and mRNA, decrease in dendritic spine density in frontal cortex, neuropil hypoplasticity, decreased GAD67 expression and decreased GABA turnover. 42 Additionally, the heterozygous reeler mutant mice exhibit decreased prepulse inhibition, 40 a phenomenon observed in schizophrenia and autism.…”

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confidence: 99%

Reelin glycoprotein: structure, biology and roles in health and disease

2004

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“…A 50% decrease in reelin protein was found in the cortex, cerebellum and hippocampus of schizophrenic and bipolar patients. 20,21 A preliminary report also described a decrease in reelin in cerebellar homogenates of autistic patients (cited in Fatemi 19 ). In addition, a form of lissencephaly was found linked to a mutation of the reelin gene in one pedigree.…”

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confidence: 99%

“…Increasing evidence suggests that the reelin protein could be involved in the pathophysiology of some major psychiatric disorders (for review, see Fatemi 19 ). A 50% decrease in reelin protein was found in the cortex, cerebellum and hippocampus of schizophrenic and bipolar patients.…”

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confidence: 99%

Absence of association between a polymorphic GGC repeat in the 5′ untranslated region of the reelin gene and autism

et al. 2002

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Autism is a complex neurodevelopmental disorder with severe cognitive and communication disabilities, that has a strong genetic predisposition. 1 Reelin, a protein involved in neuronal migration during development, is encoded by a gene located on 7q22, 2 within the candidate region on 7q showing increased allele sharing in previous genome scans. [3][4][5][6][7][8] A case/control and familybased association study recently reported a positive association between a trinucleotide repeat polymorphism (GGC) located in the 5Ј untranslated region (UTR) of the reelin gene and autism. 9 We performed a transmission disequilibrium test (TDT) analysis of the 5ЈUTR polymorphism in 167 families including 218 affected subjects (117 trios and 50 affected sib pairs) and found no evidence of linkage/association. Our results do not support previous findings and suggest that this GGC polymorphism of the reelin gene is unlikely to be a major susceptibility factor in autism and/or genetic heterogeneity.

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Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood disorders, autism and lissencephaly

Cited by 136 publications

References 65 publications

Assessment of cognitive function in the heterozygous reeler mouse

Assessment of cognitive function in the heterozygous reeler mouse

Reelin glycoprotein: structure, biology and roles in health and disease

Absence of association between a polymorphic GGC repeat in the 5′ untranslated region of the reelin gene and autism

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