Autistic Mice

What is a Mouse Model 

The goal of developing mouse models of autism is to gain a better understanding of its genetic and neurobiological basis, and to identify potential targets for therapeutic interventions.

Mouse models of autism are developed using a variety of genetic engineering techniques; the goal of these modifications is to mimic the genetic alterations that have been associated with human autism, and to study the resulting effects on behavior, brain function, and development.

• Knockout mice: insertion of specific gene or gene sequences eg: mouse that expresses a mutated version of the gene that causes alterations in protein function.
• Knock-in mice: insertion of gene eg: mouse lacks particular gene that has been linked to human autism,.
• Viral-vectors:  introduce specific genetic modifications into the mouse brain. This allows researchers to study the effects of altering gene expression or protein function in specific brain regions or cell types.

Once the mouse model has been developed, researchers can use a variety of behavioral, physiological, and molecular techniques to study the effects of the genetic modifications on brain function and behavior. This might involve measuring social behavior, communication, repetitive behaviors, or other autism-like symptoms in the mice, as well as examining brain structure, gene expression, or neurotransmitter function.

Some examples of autism mouse models:

• BTBR T+ Itpr3tf/J mice: These mice exhibit several behaviors seen in human autism, including repetitive behaviors, social deficits, and decreased communication.
• Engrailed-2 (En2) knockout mice: The En2 gene has been linked to autism in some studies. They exhibit reduced social behavior, increased repetitive behaviors, and atypical brain development.
• Neuroligin-3 (NLGN3) knockout mice: The NLGN3 gene, which has been associated with human autism. They exhibit deficits in social behavior and communication, as well as increased repetitive behaviors.
• Fragile X 1 (Fmr1) knockout mice:  Fmr1 gene is associated with fragile X syndrome, a genetic condition that may co-occur with autism. They exhibit deficits in social behavior, communication, and learning.
• Shank3 knockout mice: The Shank3 gene has been implicated in autism development. They exhibit deficits in social behavior, communication, and synaptic function.
• 16p11.2 deletion mouse model: This model is designed to mimic the human 16p11.2 microdeletion, a genetic variation that has been associated with a range of neurodevelopmental disabilites including autism. Mice with this deletion exhibit several autism-like behaviors, including reduced social interaction, repetitive behaviors, and altered vocalizations.
• Tsc2 heterozygous knockout mouse model: Tuberous sclerosis complex (TSC) is a genetic condition associated with autism. This mouse model mimics a TSC-related mutation, in which one copy of the Tsc2 gene is deleted. These mice exhibit social deficits, increased repetitive behaviors, and altered brain connectivity.
• Methyl CpG binding protein 2 (MeCP2) R306C knock-in mouse model: Mutations in the MECP2 gene have been linked to Rett syndrome, a genetic condition that shares some features with autism. This mouse model introduces a specific R306C mutation into the MeCP2 gene, leading to deficits in social interaction and communication.
• Contactin-associated protein-like 2 (Cntnap2) knockout mouse model: CNTNAP2 is a gene that has been associated with autism and language challenges. This mouse model lacks the Cntnap2 gene and exhibits social and communication deficits, as well as alterations in brain development and function.
• Oxtr -/- mouse model: Oxytocin is a hormone that plays a key role in social bonding and has been investigated as a potential treatment for autism. This mouse model lacks the gene for the oxytocin receptor and exhibits deficits in social behavior and communication.
• CNTNAP2-deficient mouse model: CNTNAP2 is a gene that has been associated with human autism. Researchers have developed a mouse model in which the Cntnap2 gene is selectively deleted, resulting in autism-like behaviors, such as reduced social interaction, altered communication, and repetitive behaviors.
• En2-deficient mouse model: En2 is a gene that is involved in the development of the cerebellum, a brain region that is known to be involved in motor coordination and cognitive processing. Mutations in the EN2 gene have been linked to human autism. Researchers have developed a mouse model in which the En2 gene is selectively deleted, resulting in autism-like behaviors, such as altered social interaction and communication.

Researchers often use multiple models to gain a more comprehensive understanding of the complex genetics and neurobiology of autism.