The interactive effects of Cyfip1 haploinsufficiency and maternal immune activation on pre-weaning social behaviour

Galloway, James 2024. The interactive effects of Cyfip1 haploinsufficiency and maternal immune activation on pre-weaning social behaviour. PhD Thesis, Cardiff University. Item availability restricted.

Preview	PDF (PhD thesis) - Accepted Post-Print Version Download (16MB) | Preview
	PDF (Cardiff University Electronic Publication Form) - Supplemental Material Restricted to Repository staff only Download (42kB)

Abstract

CYFIP1 is a gene associated with risk for autism spectrum disorders (ASD) and schizophrenia. The reasons for differing clinical outcomes when possessing CYFIP1 genetic variant remain unclear. In this current study, a Cyfip1+/- mouse model was combined with a model of infection during pregnancy, maternal immune activation (MIA), to investigate potential interactive effects on social behaviour early in development. In Chapter 3 work identifying a sub-threshold dose of poly(I:C) for use in the two-hit model, demonstrated a higher dose (10 mg/kg) produced offspring less likely to show homing behaviour at postnatal day 9 (P9) and reduced social novelty preference at P26. Effects not seen with a lower dose (5 mg/kg), the designated subthreshold dose. Chapter 4 demonstrated Cyfip1+/- interacting with MIA in a sex dependent fashion to reduce social interest in MIA Cyfip1+/- males at P9 in a homing test but not in MIA Cyfip1+/- females or control Cyfip1+/- males. At P28 all Cyfip1+/- groups showed reduced social interaction compared to wild-type (WT) littermates in a direct social interaction test. WT stimulus animals at P28 show less interest in MIA exposed WT offspring compared to Cyfip1+/- littermates and control mice, an effect not observed using the same dose in a pure WT cohort. Beyond social interaction in early development, Chapter 5 developed a novel social test, the Social Interaction Platform (SIP) which allows assessment of direct interaction between unfamiliar adult male mice. This current work provides direct and indirect evidence of interactive effects between haploinsufficiency of Cyfip1 and MIA, whilst confirming the importance of considering both experimental and stimulus animals when investigating social interaction. These findings suggest Cyfip1+/- is important for development of social behaviour and may interact with MIA, causing an earlier onset of social deficits in males, highlighting the need to interrogate social behaviour models early in development.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	8 May 2025
Last Modified:	09 May 2025 08:59
URI:	https://orca.cardiff.ac.uk/id/eprint/178164

Actions (repository staff only)

Edit Item