April 2nd of each year is "World Autism Awareness Day," aiming to increase public understanding, acceptance, and support for Autism Spectrum Disorder (ASD). Autism is not a single disease but a collection of diverse neurodevelopmental conditions, referred to as a "spectrum." Its core features primarily manifest in differences in social communication, a potentially narrow range of interests, and repetitive patterns of behavior or thinking. According to relevant research reports, the prevalence of ASD among children aged 6-12 in China is approximately 0.7%.
 

Pathogenesis
 

The pathogenesis of Autism Spectrum Disorder (ASD) is highly complex. The scientific community widely believes it results from the interaction of genetic and environmental factors. Its core mechanism can be summarized as: genetic variations trigger dysfunction in multiple pathways, amplifying neuronal damage through interactions between the "gut-brain axis" and "synapse-mitochondria," ultimately affecting the normal development of brain networks.
 

Specifically, mutations in specific genes (such as Wdr45, Atg7, Fmr1, Shank3, etc.) can lead to dysregulation of key neuronal signaling pathways like PI3K/AKT/mTOR, ERK/MAPK, JAKMIP1, and calcium signaling. These pathway abnormalities directly impair the structure and function of the postsynaptic density—including cytoskeleton organization, assembly of the postsynaptic density itself, and cellular signaling processes like glutamatergic neurotransmission. This disrupts the balance between excitatory (primarily mediated by NMDA/AMPA receptors) and inhibitory (mediated by GABA receptors) synapses in the brain, i.e., excitatory/inhibitory (E/I) balance imbalance.
 

Simultaneously, signaling pathway disruption synergizes with oxidative stress to impair mitochondrial function, leading to insufficient activation of the electron transport chain and energy metabolism disorders, which further trigger oxidative stress and neuroinflammation. On the other hand, external environmental factors, such as maternal immune activation or disruption of intestinal homeostasis (manifesting as dysbiosis, impaired gut barrier), also produce inflammatory factors or toxins. These substances enter the brain via the "gut-brain axis"—including the vagus nerve and bloodstream—exacerbating neuronal signaling pathway dysregulation and mitochondrial dysfunction.
 

Ultimately, persistent E/I imbalance, abnormal synaptic communication, and cellular energy metabolism deficits intertwine, collectively leading to abnormal connectivity and functional dysregulation in brain neural networks during development, forming the neuropathological basis of ASD.

Image source: Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

Mouse Models
 

SHANK3 Mutant Mice:​ The SHANK3 protein acts as a synaptic "scaffold," and its mutations are the primary cause of Phelan-McDermid syndrome in humans. These mice exhibit significant social avoidance, excessive grooming (stereotyped behavior), and anxiety-like behavior.
 

Fmr1 Knockout Mice:​ Model the common inherited intellectual disability, Fragile X syndrome. Mice exhibit social abnormalities, repetitive behavior, hyperactivity, and auditory hypersensitivity, primarily used to study synaptic plasticity abnormalities and for drug testing.
 

Mecp2 Mutant Mice:​ Model Rett syndrome (a neurodevelopmental disorder severely affecting girls). Mice show progressive social withdrawal, motor impairments, stereotyped behavior, and irregular breathing, used to study the role of epigenetic regulation in neurodevelopment.
 

Supporting ASD Research
 

In-depth analysis of ASD mechanisms is inseparable from animal models that can accurately mimic human disease characteristics. MingCeler Biotech, leveraging its self-developed TurboMice™ technology, has developed multiple disease mouse models. The TurboMice™ technology overcomes the technical challenges of long mouse model generation cycles and low success rates for complex models, enabling editing at almost any target gene locus. Complete homozygous gene-edited mouse models can be prepared directly from embryonic stem cells in as little as two months.
 

MingCeler Biotech​ can customize various ASD mouse models according to client needs, such as SHANK3 mutant mice, Fmr1 knockout mice, and Mecp2 mutant mice, accelerating the pace of exploration from basic research to clinical translation. Inquiries are welcome!
 

References:
 

Zhuang H, Liang Z, Ma G, Qureshi A, Ran X, Feng C, Liu X, Yan X, Shen L. Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy. MedComm (2020). 2024 Mar 2;5(3):e497. doi: 10.1002/mco2.497. PMID: 38434761; PMCID: PMC10908366.