Maternal Challenge Mouse Model of Autism
Explore how maternal stress factors can contribute to the development of autism.
The valproic acid (VPA)-induced mouse model of autism is recognized by researchers in the field for its strong face, and construct validity. It replicates core autism-like behaviors, such as impaired social interaction and repetitive actions. This model helps researchers explore underlying neurobiological mechanisms and test potential therapies, making it valuable for advancing autism spectrum disorder research.
A Model That Faithfully Recapitulates Key Elements of Autism Spectrum Disorder
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by difficulties in social interaction, communication, and the presence of restricted, repetitive patterns of behavior. The spectrum nature of the disorder means symptoms and severity vary widely between individuals. ASD typically manifests in early childhood, though its diagnosis and understanding have evolved significantly over the past decades.
The etiology of autism remains incompletely understood, though research suggests a strong genetic component. Numerous genes have been implicated, many of which are involved in synaptic function, neuronal development, and chromatin remodeling. However, no single genetic mutation accounts for the majority of cases, highlighting the polygenic and heterogeneous nature of ASD.
Environmental factors, especially those effecting the maternal environment, also contribute to autism risk, particularly when they interact with genetic predispositions. Factors such as advanced parental age, prenatal exposure to certain drugs (e.g., valproic acid), infections during pregnancy, and complications during birth have been associated with increased ASD risk. Despite extensive study, no definitive environmental cause has been universally identified, and research continues into how these factors may alter neurodevelopment.
Animal Models in Autism Research
Animal models of autism spectrum disorder, particularly rodent models, play a vital role in autism research. These models are used to investigate the genetic and neurobiological underpinnings of ASD and to test potential therapeutic interventions. Genetic models often involve the deletion or mutation of ASD-associated genes, such as SHANK3, FMR1, or MECP2, which lead to behaviors in mice that mimic some features of autism, including reduced social interaction and increased repetitive behaviors.
Environmental models also exist, such as prenatal exposure to valproic acid in rodents, which induces behavioral and neural changes reminiscent of autism. Melior runs this model of autism spectrum disorder and can provide bespoke study designs with inclusion of endpoints that best address your research goals.
Optimize Your Study with Tailored Tools and Services
Design A Mouse Model of Autism Spectrum Disorder Study That Fits Your Needs
- Evaluate Behavioral Behaviors
Social interaction (3-chamber test), repetitive behavior (marble burying test) nociceptive threshold (tail flick test)
- Measure Gene Expression Endpoints
Your gene of interest or betaine homocysteine methyl transferase (a target of VPA)
- Track Biochemical Effects
Serum homocysteine is elevated in animals with maternal VPA exposure
Ready to get the most out of your study by integrating custom services and analyses?
If you don’t see what you are looking for, contact our team of scientists to discuss your unique research goals.
We can customize your autism spectrum disorder study
Tailor your study with bespoke protocols, including 3-chamber test, marble burying behavior, tail flick test and gene expression analysis
Design your study for a prophylactic therapy (administered maternally) or therapeutically (administered to post-natal offspring subject to maternal challenge).
Interested in running a Three Chamber Test study?
The Three Chamber Test is a key tool for measuring social interaction in animal models such as mouse models of autism spectrum disorder. This test provides critical insights into key neurological elements of autism.
Publications
Nicolini, C., & Fahnestock, M. (2018). The valproic acid-induced rodent model of autism. Experimental neurology, 299, 217-227.
Sharon, G., Cruz, N. J., Kang, D. W., Gandal, M. J., Wang, B., Kim, Y. M., … & Mazmanian, S. K. (2019). Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice. Cell, 177(6), 1600-1618.
Kim, J.W.; Seung, H.; Kim, K.C.; Gonzales, E.L.T.; Oh, H.A.; Yang, S.M.; Ko, M.J.; Han, S.H.; Banerjee, S.; Shin, C.Y. Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism. Neuropharmacology 2017, 113, 71–81. [CrossRef] [PubMed]
Huang, F.; Chen, X.; Jiang, X.; Niu, J.; Cui, C.; Chen, Z.; Sun, J. Betaine ameliorates prenatal valproic-acid-induced autism-like behavioral abnormalities in mice by promoting homocysteine metabolism. Psychiatry Clin. Neurosci. 2019, 73, 317–322. [CrossRef] [PubMed]
Moy et al SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson TR, Piven J, Crawley JN, Sociability and preference for social novelty in five inbred strains: An approach to assess autistic-like behavior in mice. Genes Brain Behav. 3, 287–302 (2004). [PubMed: 15344922])
Frequently Asked Questions
Study initiation begins with pregnant females with gestation running for 28 days. Thereafter male offspring age typically aged to 28 days. With typical therapeutic treatment regimens running from 1 to 5 days and entire study can take 50-54 days but longer and shorter study designs are possible
This maternal challenge model of autism supports a range of behavioral assessments to evaluate social interaction, repeat behaviors and stimulus response, including:
- Open Field Activity
- Three chamber social interaction test
- Self grooming test
- Maximal electroshock convulsion threshold
- Marble burying test
- Sniff duration test
- Tail flick test
As well as non-behavioral assessments, including:
- Gene expression analysis
- Biochemical measurements
Yes! While commonly used to evaluate therapies to treat established autism, the maternal challenge paradigm can be used to interrogate other maternal insults that can lead to various autism spectrum disorder displays
Citations
Hirota, T., & King, B. H. (2023). Autism spectrum disorder: a review. Jama, 329(2), 157-168.
Wang, L., Wang, B., Wu, C., Wang, J., & Sun, M. (2023). Autism spectrum disorder: neurodevelopmental risk factors, biological mechanism, and precision therapy. International journal of molecular sciences, 24(3), 1819.
Varghese, M., Keshav, N., Jacot-Descombes, S., Warda, T., Wicinski, B., Dickstein, D. L., … & Hof, P. R. (2017). Autism spectrum disorder: neuropathology and animal models. Acta neuropathologica, 134, 537-566.