Autism Spectrum Disorders: Translating human deficits into mouse behavior

Pasciuto, Emanuela; Borrie, Sarah C.; Kanellopoulos, Alexandros K.; Santos, Ar R.; Cappuyns, Elisa; D’Andrea, L.; Pacini, Laura; Bagni, Claudia

doi:10.1016/j.nlm.2015.07.013

Cited by 74 publications

(69 citation statements)

References 220 publications

(243 reference statements)

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“…Several mouse models of ASD are currently available, which reproduce one or more of these core symptoms (Pasciuto et al, 2015). PTEN-KO mice showed a severe impairment in social interaction, as well as a repetitive behavior, namely upright scrambling/jumping.…”

Section: Behavioral Featuresmentioning

confidence: 99%

Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice

Cupolillo

Hoxha

Faralli

et al. 2015

Neuropsychopharmacol

125

106

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Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction, isolated areas of interest, and insistence on sameness. Mutations in Phosphatase and tensin homolog missing on chromosome 10 (PTEN) have been reported in individuals with ASDs. Recent evidence highlights a crucial role of the cerebellum in the etiopathogenesis of ASDs. In the present study we analyzed the specific contribution of cerebellar Purkinje cell (PC) PTEN loss to these disorders. Using the Cre-loxP recombination system, we generated conditional knockout mice in which PTEN inactivation was induced specifically in PCs. We investigated PC morphology and physiology as well as sociability, repetitive behavior, motor learning, and cognitive inflexibility of adult PC PTEN-mutant mice. Loss of PTEN in PCs results in autistic-like traits, including impaired sociability, repetitive behavior and deficits in motor learning. Mutant PCs appear hypertrophic and show structural abnormalities in dendrites and axons, decreased excitability, disrupted parallel fiber and climbing fiber synapses and late-onset cell death. Our results unveil new roles of PTEN in PC function and provide the first evidence of a link between the loss of PTEN in PCs and the genesis of ASD-like traits.

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Section: Behavioral Featuresmentioning

confidence: 99%

Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice

Cupolillo

Hoxha

Faralli

et al. 2015

Neuropsychopharmacol

125

106

View full text Add to dashboard Cite

show abstract

“…Deficits in learning and memory have been found in numerous mouse models of ASDs and have also been observed in mice lacking MeCP2 or MBD1 [22,31,42].…”

Section: Mbd2mentioning

confidence: 99%

“…RPM: Revolutions per minute. Tagged MBDs show distinct expression & functions Research Article anxiety-related behaviors, sociability, and learning and memory [22,31,42]. Changes in locomotor activity have been observed in Mecp2 knockout mice [31], so we quantified the locomotor activity of Mbd2 -/-mice in a home-cagelike environment.…”

Section: Mbd2mentioning

confidence: 99%

“…Impaired social interaction is a common feature of ASDs and is recapitulated in numerous mouse models [42,44]. Mice are inherently social animals and most mice prefer to interact with other mice [44].…”

Section: Mbd2mentioning

confidence: 99%

“…We found no significant difference between Mbd2 +/+ , Mbd2 +/-and Mbd2 -/-littermates in the amount of time spent sniffing the social stimulus mouse, suggesting sociability is not affected by the loss of MBD2. We next assayed nest building as an alternative test that is commonly used to assess homecage behaviors related to ASD-like phenotypes in mice [42]. We found that Mbd2 -/-mice show impaired nest-building activity in contrast to wild-type and heterozygous littermates ( Figure 1E).…”

Section: Mbd2mentioning

confidence: 99%

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Tagging Methyl-CpG-Binding Domain Proteins Reveals Different Spatiotemporal Expression and Supports Distinct Functions

et al. 2016

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Aim: DNA methylation is recognized by methyl-CpG-binding domain (MBD) proteins. Multiple MBDs are linked to neurodevelopmental disorders in humans and mice. However, the functions of MBD2 are poorly understood. We characterized Mbd2 knockout mice and determined spatiotemporal expression of MBDs and MBD2-NuRD (nucleosome remodeling deacetylase) interactions. Experimental procedures: We analyzed behavioral phenotypes, generated biotin-tagged MBD1 and MBD2 knockin mice, and performed biochemical studies of MBD2-NuRD. Results: Most behavioral measures are minimally affected in Mbd2 knockout mice. In contrast to other MBDs, MBD2 shows distinct expression patterns. Conclusion: Unlike most MBDs, MBD2 is ubiquitously expressed in all tissues examined and appears dispensable for brain functions measured in this study. We provide novel genetic tools and reveal new directions to investigate MBD2 functions in vivo.

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Basal ganglia and autism – a translational perspective

et al. 2017

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Habit learning, action selection and performance are modulated by the basal ganglia, a collection of groups of neurons located below the cerebral cortex in the brain. In autism, there is emerging evidence that parts of the basal ganglia are structurally and functionally altered disrupting normal information flow. The basal ganglia through its interconnected circuits with the cerebral cortex and the cerebellum can potentially impact various motor and cognitive functions in the autism brain.

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Autism Spectrum Disorders: Translating human deficits into mouse behavior

Cited by 74 publications

References 220 publications

Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice

Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice

Tagging Methyl-CpG-Binding Domain Proteins Reveals Different Spatiotemporal Expression and Supports Distinct Functions

Basal ganglia and autism – a translational perspective

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