Abstract
Recent genome-wide association studies (GWAS) of patient populations and genetic linkage assessments have demonstrated that the ankyrin-G (AnkG) gene is involved in neuropsychiatric disorders, including bipolar disorder, schizophrenia, and Alzheimer’s disease, but it remains unclear how the genetic variants of AnkG contribute to neuropsychiatric disorders. Here, we generated AnkG hemizygous mice using the gene trapping approach. Homozygous AnkG was embryonically lethal. Western blotting and real-time polymerase chain reaction (qPCR) assessments of wild type (WT) and AnkG +/− mutant mice demonstrated a 50% reduction of ANKG levels, at the gene and protein levels, in AnkG hemizygous mice. In behavioral tests, AnkG hemizygous mice exhibited elevated anxiety- and depression-like traits, as well as cognitive impairment. Moreover, the expression levels of cognitive-related proteins (including metabotropic glutamate receptor subtype-1, brain-derived neurotrophic factor, postsynaptic density-95, GABA-B receptor, and GABA-A receptor alpha-1) were significantly decreased (P < 0.05), suggesting a possible role for AnkG in cognition. It is possible that the loss of AnkG in the brain disrupts the excitation/inhibition balance of neurotransmitters, hindering the synaptic plasticity of neurons, and consequently leading to abnormal behavioral symptoms. Therefore, AnkG possibly contributes to neuroprotection and normal brain function, and may constitute a new target for treating neuropsychiatric diseases, especially cognitive dysfunction.
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This work was supported by the Doctorial Innovation Fund of Peking Union Medical College (2012-1001-003).
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This work was supported by the Doctorial Innovation Fund of Peking Union Medical College (2012-1001-003).
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The study protocol was approved by the Institutional Animal Care and Use Committee of the Institute of Laboratory Animal Science (Permit Number: ILAS-PLP2012-004). All experiments followed the standards for laboratory animal welfare.
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Liu, C., Zhang, L., Wu, J. et al. AnkG hemizygous mice present cognitive impairment and elevated anxiety/depressive-like traits associated with decreased expression of GABA receptors and postsynaptic density protein. Exp Brain Res 235, 3375–3390 (2017). https://doi.org/10.1007/s00221-017-5056-7
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DOI: https://doi.org/10.1007/s00221-017-5056-7