Selective behavioural impairments in mice heterozygous for the cross disorder psychiatric risk gene DLG2
| Autor: | Trevor Humby, Rachel Pass, Kerrie L. Thomas, Jeremy Hall, Lawrence Stephen Wilkinson, Niels Haan |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
medicine.medical_specialty
Heterozygote Autism Spectrum Disorder Context (language use) Anxiety Behavioral Neuroscience Mice Genetics medicine Animals Humans Bipolar disorder Habituation Psychiatry Neuronal Plasticity business.industry Tumor Suppressor Proteins Membrane Proteins medicine.disease medicine.anatomical_structure Neurology Autism spectrum disorder Schizophrenia Synaptic plasticity Motor learning business Guanylate Kinases Motor cortex |
| Zdroj: | Genes, brain, and behavior. 21(4) |
| ISSN: | 1601-183X 1601-1848 |
| Popis: | Mutations affectingDLG2are emerging as a genetic risk factor associated with neurodevelopmental psychiatric disorders including schizophrenia, autism spectrum disorder and bipolar disorder. Discs large homolog 2 (DLG2) is a member of the membrane-associated guanylate kinase protein superfamily of scaffold proteins, a component of the post-synaptic density in excitatory neurons and regulator of synaptic function and plasticity. It remains an important question whether and how haploinsuffiency of DLG2 contributes to impairments in basic behavioural and cognitive functions that may underlie symptomatic domains in patients that cross diagnostic boundaries. Using a heterozygousDlg2mouse model we examined the impact of reducedDlg2expression on functions commonly impaired in neurodevelopmental psychiatric disorders including motor co-ordination and learning, pre-pulse inhibition and habituation to novel stimuli. The heterozygousDlg2mice exhibited behavioural impairments in long-term motor learning and long-term habituation to a novel context, but not motor co-ordination, initial responses to a novel context, PPI of acoustic startle or anxiety. We additionally showed evidence for the reduced regulation of the synaptic plasticity-associated protein cFos in the motor cortex during motor learning. The sensitivity of selective behavioural and cognitive functions, particularly those dependent on synaptic plasticity, to reduced expression of DLG2 give further credence for DLG2 playing a critical role in specific brain functions but also a mechanistic understanding of symptom expression shared across psychiatric disorders. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |