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

Xiangjun Xu, Emily J Jaehne, Zarina Greenberg, Peter McCarthy, Eiman Saleh, Clare L Parish, Daria Camera, Julian Ik-Tsen Heng, Matilda Ann Haas, Bernhard T Baune, Udani Ratnayake, Maarten van den Buuse, Angel F Lopez, Hayley S Ramshaw, Quenten P Schwarz

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

Sequencing and expression analyses implicate 14-3-3 zeta as a genetic risk factor for neurodevelopmental disorders such as schizophrenia and autism. In support of this notion, we recently found that 14-3-3 zeta (-/-) 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 14-3-3 zeta (-/-) phenotype. In addition to replicating defects such as aberrant mossy fibre connectivity and impaired spatial memory, our analysis of 14-3-3 zeta (-/-) 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, 14-3-3 zeta (-/-) 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 14-3-3 zeta gives rise to many of the pathological hallmarks associated with the human condition. 14-3-3 zeta -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.
Original languageEnglish
Pages (from-to)1 - 15
Number of pages15
JournalScientific Reports
Volume5
Issue number(Art. No:12434)
DOIs
Publication statusPublished - 2015

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