The ANK3 Bipolar Disorder Gene Regulates Psychiatric-Related Behaviors That Are Modulated by Lithium and Stress

@article{Leussis2013TheAB,
  title={The ANK3 Bipolar Disorder Gene Regulates Psychiatric-Related Behaviors That Are Modulated by Lithium and Stress},
  author={Melanie P. Leussis and Erin Berry-Scott and Mai Saito and Huei-ting Jhuang and Georgius de Haan and Ozan Alkan and Catherine J. Luce and Jon M. Madison and Pamela Sklar and Thomas Serre and David E. Root and Tracey L. Petryshen},
  journal={Biological Psychiatry},
  year={2013},
  volume={73},
  pages={683-690}
}
BACKGROUND Ankyrin 3 (ANK3) has been strongly implicated as a risk gene for bipolar disorder (BD) by recent genome-wide association studies of patient populations. However, the genetic variants of ANK3 contributing to BD risk and their pathological function are unknown. METHODS To gain insight into the potential disease relevance of ANK3, we examined the function of mouse Ank3 in the regulation of psychiatric-related behaviors using genetic, neurobiological, pharmacological, and gene… Expand
Lithium reverses behavioral and axonal transport-related changes associated with ANK3 bipolar disorder gene disruption
TLDR
It is proposed that psychiatric-related behavior in Ank3+/- mice is connected to a disturbance of the kinesin cargo system, resulting in a dysfunction of neuronal ion channel and glutamate receptor transport, suggesting the promotion of anterograde kinesIn transport as part of its mechanism of action in ameliorating Ank3-related psychiatric- related behavior. Expand
The ankyrin-3 gene is associated with posttraumatic stress disorder and externalizing comorbidity
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Findings support a role of ANK3 in risk of stress-related and externalizing disorders, beyond its previous associations with bipolar disorder and schizophrenia. Expand
AnkG hemizygous mice present cognitive impairment and elevated anxiety/depressive-like traits associated with decreased expression of GABA receptors and postsynaptic density protein
TLDR
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, and may constitute a new target for treating neuropsychiatric diseases, especially cognitive dysfunction. Expand
Ankyrin-3 as a molecular marker of early-life stress and vulnerability to psychiatric disorders
TLDR
The data suggest that alterations of Ank3 expression and function may contribute to the effects of ELS on the development of psychiatric disorders, and model in humans a gene by early stress interplay on brain phenotypes during cognitive performance. Expand
Disruption of the psychiatric risk gene Ankyrin 3 enhances microtubule dynamics through GSK3/CRMP2 signaling
TLDR
The molecular effects of disrupting brain-specific Ank3 isoforms in mouse and neuronal model systems indicate that ANK3 functions in neuronal microtubule dynamics through GSK3 and its downstream substrate CRMP2. Expand
Disruption of The Psychiatric Risk Gene Ankyrin 3 Enhances Microtubule Dynamics Through GSK3/CRMP2 Signaling
TLDR
Data indicate that aNK3 functions in neuronal microtubule dynamics through GSK3 and its downstream substrate CRMP2, and reveals cellular and molecular mechanisms underlying brain-specific ANK3 disruption that may be related to its role in psychiatric illness. Expand
Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder
TLDR
A mouse model with conditional disruption of ANK3 gene in neurons in adult forebrain (Ank-G cKO) recapitulates some of the core features of human bipolar disorder and indicates that cortical microcircuitry alterations during adulthood may be involved in pathogenesis. Expand
Association analysis of ANK3 variants with bipolar disorder in the Korean population
TLDR
Haplotype analysis results suggest that ANK3 variants rs1938526 and rs10994336 may confer susceptibility for BD in the Korean population, and association analysis revealed a probable genetic difference between Korean and Caucasian populations in the degree of AnK3 involvement in BD pathogenesis. Expand
Genetic modulation of working memory deficits by ankyrin 3 gene in schizophrenia
  • Chen Zhang, Jun Cai, +8 authors Y. Fang
  • Psychology, Medicine
  • Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 2014
TLDR
The results indicated that genetic variation within ANK3 may exert gene-specific modulating effects on working memory deficits in schizophrenia. Expand
Effects of ANK3 Variation on Gray and White Matter in Bipolar Disorder
TLDR
Findings support effects of rs9804190 on frontotemporal WM in adolescents and adults with BD and suggest a mechanism contributing to WM pathology in BD. Expand
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