4.6 Article

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Journal

GENES
Volume 13, Issue 1, Pages -

Publisher

MDPI
DOI: 10.3390/genes13010028

Keywords

autism spectrum disorder; animal models; synaptopathology; neurodevelopment; sensory processing

Funding

  1. Innovative Medicines Initiative 2 Joint Undertaking [777394]
  2. European Union's Horizon 2020 research and innovation programme
  3. EFPIA
  4. SFARI
  5. Autistica
  6. AUTISM SPEAKS
  7. European Union's Horizon 2020 research and innovation programme CANDY [847818]

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Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences. It is highly heterogeneous in terms of clinical presentation, genetics, and developmental trajectories. Over a thousand genes have been implicated in ASD, leading to the generation of numerous genetic mouse models. Identifying spatial and temporal gene functions in relation to the ASD phenotype is crucial, as is finding common biological processes modulated by ASD-related genes for patient stratification and personalized treatments.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences beginning early in life. Especially sensory symptoms are highly correlated with the severity of other behavioral differences. ASD is a highly heterogeneous condition on multiple levels, including clinical presentation, genetics, and developmental trajectories. Over a thousand genes have been implicated in ASD. This has facilitated the generation of more than two hundred genetic mouse models that are contributing to understanding the biological underpinnings of ASD. Since the first symptoms already arise during early life, it is especially important to identify both spatial and temporal gene functions in relation to the ASD phenotype. To further decompose the heterogeneity, ASD-related genes can be divided into different subgroups based on common functions, such as genes involved in synaptic function. Furthermore, finding common biological processes that are modulated by this subgroup of genes is essential for possible patient stratification and the development of personalized early treatments. Here, we review the current knowledge on behavioral rodent models of synaptic dysfunction by focusing on behavioral phenotypes, spatial and temporal gene function, and molecular targets that could lead to new targeted gene-based therapy.

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