14-3-3ζ 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 Heng, Matilda Haas, Bernhard T Baune, Udani Ratnayake, Maarten van den Buuse, Angel F Lopez, Hayley S Ramshaw, Quenten Schwarz

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)12434
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 24 Jul 2015
Externally publishedYes

Keywords

  • 14-3-3 Proteins
  • Animals
  • Disease Models, Animal
  • Dopamine
  • Dopamine Plasma Membrane Transport Proteins
  • Female
  • Gene Expression
  • Lateral Ventricles
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mossy Fibers, Hippocampal
  • Pyramidal Cells
  • Schizophrenia
  • Signal Transduction
  • Spatial Memory
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this