Heterozygous loss of epilepsy gene KCNQ2 alters social, repetitive and exploratory behaviors

Content Provider	Scilit
Author	Kim, Eung Chang Patel, Jaimin Zhang, Jiaren Soh, Heun Rhodes, Justin S. Tzingounis, Anastasios V. Chung, Hee Jung
Copyright Year	2019
Description	Journal: Genes, Brain and Behavior $KCNQ/K_{v}$7 channels conduct voltage‐dependent outward potassium currents that potently decrease neuronal excitability. Heterozygous inherited mutations in their principle subunits $K_{v}$7.2/KCNQ2 and $K_{v}$7.3/KCNQ3 cause benign familial neonatal epilepsy whereas patients with de novo heterozygous $K_{v}$7.2 mutations are associated with early‐onset epileptic encephalopathy and neurodevelopmental disorders characterized by intellectual disability, developmental delay, and autism. However, the role of $K_{v}$7.2‐containing $K_{v}$7 channels in behaviors especially autism‐associated behaviors has not been described. Since pathogenic $K_{v}$7.2 mutations in patients are typically heterozygous loss‐of‐function mutations, we investigated the contributions of $K_{v}$7.2 to exploratory, social, repetitive, and compulsive‐like behaviors by behavioral phenotyping of both male and female $KCNQ2^{+/‐}$ mice that were heterozygous null for the KCNQ2 gene. Compared to their wild‐type littermates, male and female $KCNQ2^{+/‐}$ mice displayed increased locomotor activity in their home cage during the light phase but not the dark phase and showed no difference in motor coordination, suggesting hyperactivity during the inactive light phase. In the dark phase, $KCNQ2^{+/‐}$ group showed enhanced exploratory behaviors, and repetitive grooming but decreased sociability with sex differences in the degree of these behaviors. While male $KCNQ2^{+/‐}$ mice displayed enhanced compulsive‐like behavior and social dominance, female $KCNQ2^{+/‐}$ mice did not. In addition to elevated seizure susceptibility, our findings together indicate that heterozygous loss of $K_{v}$7.2 induces behavioral abnormalities including autism‐associated behaviors such as reduced sociability and enhanced repetitive behaviors. Therefore, our study is the first to provide a tangible link between loss‐of‐function $K_{v}$7.2 mutations and the behavioral comorbidities of $K_{v}$7.2‐associated epilepsy.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050516/pdf
e-ISSN	1601183X
DOI	10.1111/gbb.12599
Journal	Genes, Brain and Behavior
Issue Number	1
Volume Number	19
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2019-07-08
Access Restriction	Open
Subject Keyword	Journal: Genes, Brain and Behavior Social Interaction
Content Type	Text
Resource Type	Article