Behavioural abnormalities in a novel mouse model for Silver Russell Syndrome

McNamara, Grainne Iseult, Davis, Brittany Ann, Dwyer, Dominic Michael ORCID: https://orcid.org/0000-0001-8069-5508, John, Rosalind M. ORCID: https://orcid.org/0000-0002-3827-7617 and Isles, Anthony Roger ORCID: https://orcid.org/0000-0002-7587-5712 2016. Behavioural abnormalities in a novel mouse model for Silver Russell Syndrome. Human Molecular Genetics 25 (24) , pp. 5407-5417. 10.1093/hmg/ddw357

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Abstract

Silver Russell Syndrome (SRS) syndrome is an imprinting disorder involving low birth weight with complex genetics and diagnostics. Some rare SRS patients carry maternally inherited microduplications spanning the imprinted genes CDKN1C, PHLDA2, SLC22A18 and KCNQ1, suggesting that overexpression of one of more of these genes contributes to the SRS phenotype. While this molecular alteration is very rare, feeding difficulties are a very common feature of this condition. Given that SRS children also have very low body mass index, understanding the underpinning biology of the eating disorder is important, as well as potential co-occurring behavioural alterations. Here, we report that a mouse model of this microduplication exhibits a number of behavioural deficits. The mice had a blunted perception of the palatability of a given foodstuff. This perception may underpin the fussiness with food. We additionally report hypoactivity, unrelated to anxiety or motoric function, and a deficit in appropriate integration of incoming sensory information. Importantly, using a second genetic model, we were able to attribute all altered behaviours to elevated expression of a single gene, Cdkn1c. This is the first report linking elevated Cdkn1c to altered behaviour in mice. Importantly, the findings from our study may have relevance for SRS and highlight a potentially underreported aspect of this disorder.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Biosciences Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
Publisher:	Oxford University Press
ISSN:	0964-6906
Funders:	Wellcome Trust
Date of First Compliant Deposit:	2 November 2016
Date of Acceptance:	16 October 2016
Last Modified:	19 Jan 2024 07:18
URI:	https://orca.cardiff.ac.uk/id/eprint/95796

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