Animal Models of Autism
Abbigail Higgins
Why use animal models?
Much of the research on autism is difficult to test on humans. This can be due to factors like an individuals unwillingness to participate in a task. Testing treatments on individuals with more apparent symptoms tends to yeild more obvious results, however those individuals are also more likely to have sensory or cognitive issues that make them unwilling to participate (See Genetic and Epigenetic Contributions to autism for more information on autism in humans). Much of the treatments are also highly experimental. To help us further research on autism we use various different animals, from non-human primates to dogs, cattle, rodents, zebrafish, birds, bees, and even more (Li et al. 2021). Each of these have different pro’s and con’s. Animals which are more closely related to humans (such as other primates and dogs) tend to be much more expensive and difficult to obtain, however are more accurate to human physiology. Animals which are less related (such as bees and zebrafish) still have great value in research, due to their low cost and stereotypical behaviors
Genetic Models
Genetic models of ASD tend to be popular due to the evidence of autism being a genetic disorder, with more than 200 genes used to form these animal models (Li et al. 2021). This type of model is effective for testing pharmasuticles. Gene-editing technologies, such as CRISPR/Cas9, make this sort of model possible. Because we do not know the exact genes that cause autism, most genetic models use gene modifications that cause a symptomology resembling autism rather than autism itself. Many of these models, such as NRXN knockout mice, will also elicit symptoms of simular or comorbid disorders (like ADHD or Rett syndrome). MECP2, FMR1, SHANK3, TSC1/2, UBE3A, NLGNs, CHD8, POGZ, ANK2, MIR137, and 16p11.2 are some of the most common modifications, each of which has its own particular effects and circumsances.
Enviornmentally Induced Models
There is also evidence in enviornmental factors causing autism in humans, and using these models tends to be a cheaper and faster method of research. VPA, PPA, BPA, MIA, BDV, GM, and RCS are all common materials used to enviornmentally ilicit autism syptoms, often through pathways causing oxydative stress. These models are being used often in more recent research, especially VPA (valproic acid) which is generally given to female mice during pregnancy, though has also been seen to be effective postnatally (Li et al. 2021).
Idiopathic Models
This model of autism is represented by specific strains of mice that are selevtively bred to naturally have autism characteristics (Li et al. 2021). This gives the benefit of being able to have an animal that more acurately resembles all of the parts of ASD, however not without downside. Using animals like this makes typical controls less simular in comparison to using the same line of animal and modifying only part of them. This does make tests more simular to the variation seen in human tests however, and each these attributes are weighed when determining what model to use.
Where this research is going
Though we have many different animal models of autism, each and every one has its differing good and bad. There is currently no one model that perfectly represents autism in humans, so alongside research on treatments themselves, there is much to be researched on animal models of autism. We currently do not have any drug treatment that is able to help with all of ASD symptoms, though we have found much to help certain parts of autism. Treatments like oxytosin gut microbiota have been shown to improve several of ASDs symptoms, and clinically many medications for other disorders are prescribed to help particular symptoms (Li et al. 2021). Drugs such as GABAB or Histine H3 receptor agonists have been shown to greatly reduce symptoms in some of our animal models, so we have some promising treatments to look forward to, with ASD being a heavily researched disorder (Jiang et al. 2022, Taheri et al. 2022).
Jiang, S., Xiao, L., Sun, Y., He, M., Gao, C., Zhu, C., Chang, H., Ding, J., Li, W., Wang, Y., Sun, T., & Wang, F. (2022). The GABAB receptor agonist STX209 reverses the autism-like behaviour in an animal model of autism induced by prenatal exposure to valproic acid. Molecular Medicine Reports, 25(5). http://dx.doi.org.hal.weber.edu:2200/10.3892/mmr.2022.12670
Taheri, F., Esmaeilpour, K., Sepehri, G., Sheibani, V., ur Rehman, N., & Maneshian, M. (2022). Histamine H3 receptor antagonist, ciproxifan, alleviates cognition and synaptic plasticity alterations in a valproic acid-induced animal model of autism. Psychopharmacology, 239(8), 2673+. http://dx.doi.org.hal.weber.edu:2200/10.1007/s00213-022-06155-z