14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders

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dc.contributor.authorXu, X.
dc.contributor.authorJaehne, E.
dc.contributor.authorGreenberg, Z.
dc.contributor.authorMcCarthy, P.
dc.contributor.authorSaleh, E.
dc.contributor.authorParish, C.
dc.contributor.authorCamera, D.
dc.contributor.authorHeng, J.
dc.contributor.authorHaas, M.
dc.contributor.authorBaune, B.
dc.contributor.authorRatnayake, U.
dc.contributor.authorVan Den Buuse, M.
dc.contributor.authorLopez, A.
dc.contributor.authorRamshaw, H.
dc.contributor.authorSchwarz, Q.
dc.date.issued2015
dc.description.abstractSequencing and expression analyses implicate 14-3-3ζ as a genetic risk factor for neurodevelopmental disorders such as schizophrenia and autism. In support of this notion, we recently found that 14-3-3ζ(-/-) mice in the Sv/129 background display schizophrenia-like defects. As epistatic interactions play a significant role in disease pathogenesis we generated a new congenic strain in the BALB/c background to determine the impact of genetic interactions on the 14-3-3ζ(-/-) phenotype. In addition to replicating defects such as aberrant mossy fibre connectivity and impaired spatial memory, our analysis of 14-3-3ζ(-/-) BALB/c mice identified enlarged lateral ventricles, reduced synaptic density and ectopically positioned pyramidal neurons in all subfields of the hippocampus. In contrast to our previous analyses, 14-3-3ζ(-/-) BALB/c mice lacked locomotor hyperactivity that was underscored by normal levels of the dopamine transporter (DAT) and dopamine signalling. Taken together, our results demonstrate that dysfunction of 14-3-3ζ gives rise to many of the pathological hallmarks associated with the human condition. 14-3-3ζ-deficient BALB/c mice therefore provide a novel model to address the underlying biology of structural defects affecting the hippocampus and ventricle, and cognitive defects such as hippocampal-dependent learning and memory.
dc.description.statementofresponsibilityXiangjun Xu, Emily J. Jaehne, Zarina Greenberg, Peter McCarthy, Eiman Saleh, Clare L. Parish, Daria Camera, Julian Heng, Matilda Haas, Bernhard T. Baune, Udani Ratnayake, Maarten van den Buuse, Angel F. Lopez, Hayley S. Ramshaw, Quenten Schwarz
dc.identifier.citationScientific Reports, 2015; 5(1):12434-1-12434-15
dc.identifier.doi10.1038/srep12434
dc.identifier.issn2045-2322
dc.identifier.issn2045-2322
dc.identifier.orcidJaehne, E. [0000-0003-0532-1623]
dc.identifier.orcidBaune, B. [0000-0001-6548-426X]
dc.identifier.orcidLopez, A. [0000-0001-7430-0135]
dc.identifier.orcidRamshaw, H. [0000-0001-9909-282X]
dc.identifier.urihttp://hdl.handle.net/2440/94216
dc.language.isoen
dc.publisherNature
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
dc.source.urihttps://doi.org/10.1038/srep12434
dc.subjectDevelopment disorders
dc.subjectNeuronal development
dc.title14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders
dc.title.alternative14-3-3zeta deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders
dc.typeJournal article
pubs.publication-statusPublished

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