Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities and core autism-related deficits

By O. Peñagarikano, B. Abrahams, Edward I. Herman, Kellen D. Winden, Amos Gdalyahu, Hongmei Dong, L. Sonnenblick, R. Gruver, Joel Almajano, Anatol Bragin and 4 more. Cell, 2011

1,020 citations recorded by the source corpus.

SUMMARY Although many genes predisposing to autism spectrum disorders (ASD) have been identified, the biological mechanism(s) remain unclear. Mouse models based on human disease-causing mutations provide the potential for understanding gene function and novel treatment development. Here we characterize a mouse knockout of the Cntnap2 gene, which is strongly associated with ASD and allied neurodevelopmental disorders. Cntnap2−/− mice show deficits in the three core ASD behavioral domains, as well as hyperactivity and epileptic seizures, as has been reported in humans with CNTNAP2 mutations. Neuropathological and physiological analyses of these mice before the onset of seizures reveal neuronal migration abnormalities, reduced number of interneurons and abnormal neuronal network activity. In addition, treatment with the FDA approved drug risperidone, ameliorates the targeted repetitive behaviors in the mutant mice. These data demonstrate a functional role for CNTNAP2 in brain development and provide a new tool for mechanistic and therapeutic research in ASD.

Subfields: Cognitive Neuroscience, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/894ba860ad739e5404e8c3c30fa34c60427842bd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cognitive Neuroscience

1. Paul M. Thompson
2. Arthur W. Toga
3. Mirella Dapretto
4. Susan Y. Bookheimer
5. Jesse A. Brown
6. Jeff D. Rudie
7. Nicholas G. Martin
8. P. Patterson

In Genetics

1. Paul M. Thompson
2. Dan R. Littman
3. P. Patterson
4. G. Choi

In Molecular Biology

1. Paul M. Thompson
2. Arthur W. Toga
3. Dan R. Littman
4. G. Choi

Citations in the corpus

• The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring (2016, background): “Furthermore it is worthwhile to note that the loss of certain genes that induce ASD-like phenotypes were also found with defects in cortical lamination (41, 42).”
• Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2 (2011, positive): “A recent study characterizing CNTNAP2 knockout mice found behavioral deficits characteristic of autism—namely, seizures—as well as neuronal migration abnormalities, reduced interneuron density, and abnormal neuronal network activity (Pen˜agarikano et al., 2011).”
• Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism (2012, background): “, 2010), and in reelin, Mecp-2 and CNTNAP2 mutant mice (Ognibene et al., 2007; De Filippis et al., 2010; Peñagarikano et al., 2011).”
• The microbiota modulates gut physiology and behavioral abnormalities associated with autism (2013, neutral): “Selective amelioration of ASD-related behaviors is also seen with risperidone treatment of CNTNAP2 knockout mice, a genetic mouse model for ASD (Peñagarikano et al., 2011), wherein communicative and repetitive, but not social, behavior is corrected.”