PT  - JOURNAL ARTICLE
AU  - Sophie Waldron
AU  - Rachel Pass
AU  - Simonas Griesius
AU  - Jack R. Mellor
AU  - Emma S. J. Robinson
AU  - Kerrie L. Thomas
AU  - Lawrence S. Wilkinson
AU  - Trevor Humby
AU  - Jeremy Hall
AU  - Dominic M. Dwyer
TI  - Behavioural and molecular characterisation of the Dlg2 haploinsufficiency rat model of genetic risk for psychiatric disorder
AID  - 10.1101/2021.10.11.463943
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.11.463943
4099  - http://biorxiv.org/content/early/2021/10/12/2021.10.11.463943.short
4100  - http://biorxiv.org/content/early/2021/10/12/2021.10.11.463943.full
AB  - Genetic studies implicate disruption to the DLG2 gene in copy number variants as increasing risk for schizophrenia, autism spectrum disorders and intellectual disability. To investigate psychiatric endophenotypes associated with DLG2 haploinsufficiency (and concomitant PSD-93 protein reduction) a novel clinically relevant Dlg2+/- rat was assessed for abnormalities in anxiety, sensorimotor gating, hedonic reactions, social behaviour, and locomotor response to the N-Methyl-D-aspartic acid receptor antagonist phencyclidine. Dlg gene and protein expression were also investigated to assess model validity. Reductions in PSD-93 messenger RNA and protein were observed in the absence of compensation by other related genes or proteins. Behaviourally Dlg2+/- rats show potentiated locomotor response to phencyclidine, as is typical of psychotic disorder models, in the absence of deficits in the other behavioural phenotypes assessed here. This shows that the behavioural effects of Dlg2 haploinsufficiency may specifically relate to psychosis vulnerability but are subtle, providing a contrast to the gross deficits in Dlg2 homozygous models (Winkler, et al., 2018; Yoo et al., 2020a) which do not so specifically model the single chromosome DLG2 deletion in carriers of risk-associated copy number variants.Competing Interest StatementThe authors have declared no competing interest.