Understanding intellectual disability and autism spectrum disorders from common mouse models: synapses to behaviour

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Neurodevelopmental disorders (NDDs), including intellectual disability (ID) and autism spectrum disorders (ASDs), affect millions globally.
• These conditions arise from disruptions in normal brain development, necessitating a deeper understanding of their underlying mechanisms.

Purpose of the Study:

• To review studies using mouse models of major monogenic causes of ID and ASDs.
• To identify convergent pathological pathways despite diverse genetic origins.
• To explore therapeutic strategies targeting these common pathways.

Main Methods:

• Analysis of existing literature on mouse models for five key genes: Fmr1, Syngap1, Mecp2, Shank2/3, and Neuroligins/Neurnexins.
• Comparative study of phenotypic outcomes and molecular underpinnings.

Main Results:

• Mutations in these genes, though diverse, converge on shared etiological pathways.
• This convergence results in characteristic cognitive, social, and emotional deficits observed in ID and ASDs.
• Mouse models demonstrate the potential for both pharmacological and genetic therapies to restore function.

Conclusions:

• Common pathological nodes exist for ID and ASDs, offering promising therapeutic targets.
• Mouse models are valuable tools for investigating NDDs and testing novel treatments.
• Functional recovery through advanced therapies is achievable in NDD models.