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- Title
14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders.
- Authors
Xu, Xiangjun; Greenberg, Zarina; McCarthy, Peter; Saleh, Eiman; Lopez, Angel F.; Ramshaw, Hayley S.; Schwarz, Quenten; Jaehne, Emily J.; Baune, Bernhard T.; Parish, Clare L.; Ratnayake, Udani; Camera, Daria; Heng, Julian; Haas, Matilda; Buuse, Maarten van den
- Abstract
Sequencing 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.
- Subjects
14-3-3 proteins; BRAIN diseases; DEVELOPMENTAL disabilities; PROTEIN expression; MICE anatomy; MICE behavior; DOPAMINE; GENETICS
- Publication
Scientific Reports, 2015, p12434
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep12434