Viewing Animal Models for Tuberous Sclerosis Complex in the Light of Evolution

Howe, Christopher J.; Serfontein, Jaco; Nisbet, R. Ellen R.; de Vries, Petrus J.

Abstract

Tuberous sclerosis complex (TSC) is a multisystem disorder usually caused by a mutation in either the TSC1 or TSC2 genes. Approximately 50 % of individuals with TSC develop an autism spectrum disorder. Between 1 and 4 % of autism is attributable to tuberous sclerosis. TSC is therefore one of the medical conditions most consistently associated with autism spectrum disorder (ASD), and thus represents a good model to study the genetic and molecular determinants of autism. A number of experimental organisms have been used as model systems for TSC. We review briefly the structure and function of the TSC1 and TSC2 proteins, and their distribution among different evolutionary groups. We review the organisms used to provide genetic models for TSC, notably Schizosaccharomyces pombe (fission yeast), Candida albicans, Drosophila melanogaster (fruit fly), Danio rerio (zebra fish), Mus musculus (mouse), and Rattus norvegicus (rat). We discuss whether the mutations used are appropriate models for the mutations seen in human examples of TSC, and whether the nonhuman proteins are accurate models for all the structural and functional features of the human proteins. We also discuss the appropriateness of these organisms as models for human cognitive functions. Current evidence suggests that rat and mouse are good model organisms from an evolutionary perspective. However, the mutations used represent only a small sample of the diversity of mutations seen in human TSC, and this diversity may be responsible for the variability of features seen in affected people.

Citation

Howe, C. J., Serfontein, J., Nisbet, R. E. R., & de Vries, P. J. (2015). Viewing Animal Models for Tuberous Sclerosis Complex in the Light of Evolution. In Organism Models of Autism Spectrum Disorders (99-115). Springer New York. https://doi.org/10.1007/978-1-4939-2250-5_4

• Online Publication Date: Dec 22, 2014
• Publication Date: 2015
• Deposit Date: Jun 15, 2020
• Pages: 99-115
• Series Title: Neuromethods
• Series Number: 100
• Book Title: Organism Models of Autism Spectrum Disorders
• ISBN: 9781493922499
• DOI: https://doi.org/10.1007/978-1-4939-2250-5_4
• Public URL: https://nottingham-repository.worktribe.com/output/4654864