Advances in behavioral genetics: mouse models of autism

Abstract

Autism is a neurodevelopmental syndrome with markedly high heritability. The diagnostic indicators of autism are core behavioral symptoms, rather than definitive neuropathological markers. Etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In this review, we focus on genetic pathways with multiple members represented in autism candidate gene lists. Many of these pathways can also be impinged upon by environmental risk factors associated with the disorder. The mouse model system provides a method to experimentally manipulate candidate genes for autism susceptibility, and to use environmental challenges to drive aberrant gene expression and cell pathology early in development. Mouse models for fragile X syndrome, Rett syndrome and other disorders associated with autistic-like behavior have elucidated neuropathology that might underlie the autism phenotype, including abnormalities in synaptic plasticity. Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, relevant to findings in autistic populations. Advances have included the evaluation of mouse models with behavioral assays designed to reflect disease symptoms, including impaired social interaction, communication deficits and repetitive behaviors, and the symptom onset during the neonatal period. Research focusing on the effect of gene-by-gene interactions or genetic susceptibility to detrimental environmental challenges may further understanding of the complex etiology for autism.

Autoimmune Disorder and Autism

“…In addition, there is another group of models constructed by surgical or toxic treatments of candidate regions in the brain, in general during development [255]. Some other reports regarding autistic-like behaviors in BALB/c and A/J mice have also been seen [250,[256][257][258].…”

“…Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, which are relevant to findings in autistic subjects [250]. These models have elucidated neuropathology that might underlie the autism phenotype.…”

“…These models have elucidated neuropathology that might underlie the autism phenotype. There are currently several mouse models for autism research, most of which are primarily developed by knocking out different candidate genes for other neuropsychiatric diseases such as fragile X syndrome [250,251], Rett syndrome [252], but now are used as autistic models because of their autistic-like behaviors. Other examples include Engrailed 1&2 and PTEN genetic mice [253,254].…”

New mouse genetic model duplicates human 15q11–13 autistic phenotypes, or does it?

“…Although this new mouse model phenocopies relevant autism symptoms, it remains to be determined whether this chromosome duplication involves additional molecular mechanisms that affect synapse formation, balancing of neural networks, and the formation of behaviorally-relevant neurocircuitries. These are fundamental processes in autism etiology and have been validated previously in single-gene autism mouse models (Moy and Nadler, 2008). Considering the existence of multiple 15q11-13 autism risk genes that affect synapse formation (e.g.…”

“…These candidate genes were identified through human genetic association or linkage studies, or by studying mutations that involve pathways that are potentially altered in autism (Moy and Nadler, 2008;Levitt and Campbell, 2009 Weyden and Bradley, 2006). In issue 137 of Cell, Nakatani et al reported the first targeted chromosomal duplication in a mouse model of the human 15q11-13 duplication that is associated with autism (Nakatani et al, 2009).…”