The mouse Engrailed genes: A window into autism

Abstract

The complex behavioral symptoms and neuroanatomical abnormalities observed in autistic individuals strongly suggest a multi-factorial basis for this perplexing disease. Although not the perfect model, we believe the Engrailed genes provide an invaluable "window" into the elusive etiology of Autism Spectrum Disorder. The Engrailed-2 gene has been associated with autism in genetic linkage studies. The En2 knock-out mouse harbors cerebellar abnormalities that are similar to those found in autistic individuals and, as we report here, has a distinct anterior shift in the position of the amygdala in the cerebral cortex. Our initial analysis of background effects in the En1 mouse knock-out provides insight as to possible molecular mechanisms and gender differences associated with autism. These findings further the connection between Engrailed and autism and provide new avenues to explore in the ongoing study of the biological basis of this multifaceted disease.

Advances in behavioral genetics: mouse models of autism

“…301,302 The cerebellar neuropathology emerges during embryonic development of the mutant mice. 303 In a recent report and overview, Kuemerle et al 299 note that the En2-null mice also evidence an anterior shift in the position of amygdalar nuclei, which may reflect a similar shift observed in a rat model for prenatal exposure to valproic acid. Disturbances in cerebellar development have been associated with deletion of another gene located on chromosome 7q, FOXP2.…”

“…[296][297][298] En2 deletion animals have behavioral and neuroanatomical abnormalities that reflect alterations in autism. 15,299 For example, both juvenile and adult En2-null mice show deficits in social interaction. 34 The mutant mice are also characterized by hyperactivity, reduced spatial learning 34 and impaired motor coordination.…”

Engrailed-2 regulates genes related to vesicle formation and transport in cerebellar Purkinje cells

“…Based on expression profiles of normal brain, the amygdala is an interesting region where this pathway can be operative. The amygdala co-expresses Engrailed, the oxytocin receptor, and Cck (Kuemerle et al, 2006;Huber et al, 2005;Mascagni and McDonald, 2003), and it is considered to be strongly involved in ASD (Schulkin, 2007).…”

Autoimmune Disorder and Autism

“…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]. 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].…”