Animal model of autism

The development of an animal model of autism is one approach researchers use to study potential causes of autism.[1] Given the complexity of autism and its etiology, researchers often focus only on single features of autism when using animal models.[2]

Rodent model

One of the more common rodent models is the Norway rat (Rattus norvegicus).[3] More recent research has used the house mouse (Mus musculus) to model autism because it is a social species. Other strains of mice used include mu opioid receptor knockout mice, as well as Fmr1 knockout mice; the latter are also used as animal models of Fragile X syndrome.[4]

The Norway rat has been used, for example, by Mady Hornig to implicate thiomersal in autism.[5][6] The current scientific consensus is that no convincing scientific evidence supports these claims,[7][8] and major scientific and medical bodies such as the Institute of Medicine[7] and World Health Organization[9] (WHO) as well as governmental agencies such as the U.S. Food and Drug Administration[10] (FDA) and Centers for Disease Control and Prevention[11] (CDC) reject any role for thiomersal in autism or other neurodevelopmental disorders.

Behaviors measured in these models include "approach to olfactory pheromones emitted by other mice, approach to familiar and new conspecifics, reciprocal social interactions, ultrasonic vocalizations, communal nesting, sexual and parenting behaviors, territorial scent marking, and aggressive behaviors."[12] Social interaction is measured by how the mouse interacts with a stranger mouse introduced in the opposite side of a test box.[13]

Researchers from the University of Florida have used deer mice to study restricted and repetitive behavior such as compulsive grooming, and how these behaviors may be caused by specific gene mutations.[14] In addition, Craig Powell of the University of Texas Southwestern Medical Center, with a grant from Autism Speaks,[15] is currently using mice to examine the potential role of neuroligin gene mutations in causing autism. Much research has been done into the use of a rat model to show how Borna virus infection,[16][17] exposure to valproic acid in utero,[18] and maternal immune activation[19] may cause autism.

Another goal of the use of rodent models to study autism is to identify the mechanism by which autism develops in humans.[1] Other researchers have developed an autism severity score to measure the degree of severity of the mice's autism, as well as the use of scent marking behavior[20] and vocalization distress[13] as models for communication.

It has been observed that mice lacking the gene for oxytocin exhibit deficits in social interaction, and that it may be possible to develop treatments for autism based on abnormalities in this and other neuropeptides.[21][22]

Songbird model

In 2012, a researcher from the University of Nebraska at Kearney published a study reviewing research that had been done using the songbird as a model for autism spectrum disorders, noting that the neurobiology of vocalization is similar between humans and songbirds, and that, in both species, social learning plays a central role in the development of the ability to vocalize.[23] Other research using this model has been done by Stephanie White at the University of California Los Angeles, who studied mutations in the FOXP2 gene and its potential role in learned vocalization in both songbirds (specifically the zebra finch) and humans.[24][25]

Controversy

In 2013, a study was published by Swiss researchers which concluded that 91% (31 out of the 34 studies reviewed) of valproic acid-autism studies using animal models suffered from statistical flaws—specifically, they had failed to correctly use the litter as a level of statistical analysis rather than just the individual (i.e., an individual mouse or rat).[26][27]

References

  1. 1 2 Bourgeron, T.; Jamain, S. P.; Granon, S. (2006). "Animal Models of Autism". Transgenic and Knockout Models of Neuropsychiatric Disorders. Contemporary Clinical Neuroscience. p. 151. doi:10.1007/978-1-59745-058-4_8. ISBN 978-1-58829-507-1.
  2. ↑ Dicicco-Bloom, E.; Lord, C.; Zwaigenbaum, L.; Courchesne, E.; Dager, S. R.; Schmitz, C.; Schultz, R. T.; Crawley, J.; Young, L. J. (2006). "The Developmental Neurobiology of Autism Spectrum Disorder". Journal of Neuroscience. 26 (26): 6897–6906. doi:10.1523/JNEUROSCI.1712-06.2006. PMID 16807320.
  3. ↑ Callaway, E. (2011). "Rat models on the rise in autism research". Nature. doi:10.1038/nature.2011.9415.
  4. ↑ Oddi, D.; Crusio, W. E.; d'Amato, F. R.; Pietropaolo, S. (2013). "Monogenic mouse models of social dysfunction: Implications for autism". Behavioural Brain Research. 251: 75–84. doi:10.1016/j.bbr.2013.01.002. PMID 23327738.
  5. ↑ Vaccine Links to Autism?
  6. ↑ Hornig, M.; Chian, D.; Lipkin, W. I. (2004). "Neurotoxic effects of postnatal thimerosal are mouse strain dependent". Molecular Psychiatry. 9 (9): 833–845. doi:10.1038/sj.mp.4001529. PMID 15184908.
  7. 1 2 Immunization Safety Review Committee, Board on Health Promotion and Disease Prevention, Institute of Medicine (2004). Immunization Safety Review: Vaccines and Autism. Washington, DC: The National Academies Press. ISBN 0-309-09237-X.
  8. ↑ Doja A, Roberts W (2006). "Immunizations and autism: a review of the literature". Can J Neurol Sci. 33 (4): 341–6. doi:10.1017/s031716710000528x. PMID 17168158.
  9. ↑ World Health Organization (2006). "Thiomersal and vaccines: questions and answers". Retrieved 2009-05-19.
  10. ↑ "Thimerosal in vaccines". Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. 2008-06-03. Retrieved 2008-07-25.
  11. ↑ Centers for Disease Control (2008-02-08). "Mercury and vaccines (thimerosal)". Retrieved 2011-08-01.
  12. ↑ Crawley, J. N. (2012). "Translational animal models of autism and neurodevelopmental disorders". Dialogues in clinical neuroscience. 14 (3): 293–305. PMC 3513683Freely accessible. PMID 23226954.
  13. 1 2 Klauck, S. M.; Poustka, A. (2006). "Animal models of autism". Drug Discovery Today: Disease Models. 3 (4): 313. doi:10.1016/j.ddmod.2006.11.005.
  14. ↑ Lewis, M.; Tanimura, Y.; Lee, L.; Bodfish, J. (2007). "Animal models of restricted repetitive behavior in autism". Behavioural Brain Research. 176 (1): 66–74. doi:10.1016/j.bbr.2006.08.023. PMC 3709864Freely accessible. PMID 16997392.
  15. ↑ Animal Models of Autism: Pathogenesis and Treatment
  16. ↑ Libbey, J.; Sweeten, T.; McMahon, W.; Fujinami, R. (2005). "Autistic disorder and viral infections". Journal of NeuroVirology. 11 (1): 1–10. doi:10.1080/13550280590900553. PMID 15804954.
  17. ↑ Pletnikov, M. V.; Moran, T. H.; Carbone, K. M. (2002). "Borna disease virus infection of the neonatal rat: Developmental brain injury model of autism spectrum disorders". Frontiers in Bioscience. 7: d593–d607. doi:10.2741/pletnik. PMID 11861216.
  18. ↑ Roullet, F. I.; Lai, J. K. Y.; Foster, J. A. (2013). "In utero exposure to valproic acid and autism — A current review of clinical and animal studies". Neurotoxicology and Teratology. 36: 47–56. doi:10.1016/j.ntt.2013.01.004. PMID 23395807.
  19. ↑ Parker-Athill, E. C.; Tan, J. (2010). "Maternal Immune Activation and Autism Spectrum Disorder: Interleukin-6 Signaling as a Key Mechanistic Pathway". Neurosignals. 18 (2): 113–128. doi:10.1159/000319828. PMC 3068755Freely accessible. PMID 20924155.
  20. ↑ Wöhr, M.; Scattoni, M. L. (2013). "Behavioural methods used in rodent models of autism spectrum disorders: Current standards and new developments". Behavioural Brain Research. 251: 5–17. doi:10.1016/j.bbr.2013.05.047. PMID 23769995.
  21. ↑ Lim, M. M.; Bielsky, I. F.; Young, L. J. (2005). "Neuropeptides and the social brain: Potential rodent models of autism". International Journal of Developmental Neuroscience. 23 (2–3): 235–243. doi:10.1016/j.ijdevneu.2004.05.006. PMID 15749248.
  22. ↑ Chadman, K. K.; Guariglia, S. R.; Yoo, J. H. (2012). "New directions in the treatment of autism spectrum disorders from animal model research". Expert Opinion on Drug Discovery. 7 (5): 407–416. doi:10.1517/17460441.2012.678828. PMID 22494457.
  23. ↑ Panaitof, S. C. (2012). "A songbird animal model for dissecting the genetic bases of autism spectrum disorder". Disease markers. 33 (5): 241–249. doi:10.3233/DMA-2012-0918. PMID 22960335.
  24. ↑ Finding an Animal Model for Language Development
  25. ↑ Condro, M. C.; White, S. A. (2014). "Distribution of language-related Cntnap2 protein in neural circuits critical for vocal learning". Journal of Comparative Neurology. 522: 169. doi:10.1002/cne.23394.
  26. ↑ Lazic, S. E.; Essioux, L. (2013). "Improving basic and translational science by accounting for litter-to-litter variation in animal models". BMC Neuroscience. 14: 37. doi:10.1186/1471-2202-14-37. PMC 3661356Freely accessible. PMID 23522086.
  27. ↑ Varughese, Ansa (2 April 2013). "New Study Says 91% Of Autism Studies Using Certain Animal Models Are Statistically Flawed". Medical Daily. Retrieved 10 December 2013.
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