14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders.
Scientific Reports, July 2015
Xu, Xiangjun, Jaehne, Emily J, Greenberg, Zarina, McCarthy, Peter, Saleh, Eiman, Parish, Clare L, Camera, Daria, Heng, Julian, Haas, Matilda, Baune, Bernhard T, Ratnayake, Udani, Buuse, Maarten van den, Lopez, Angel F, Ramshaw, Hayley S, Schwarz, Quenten, Xiangjun 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
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.
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