title: 14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders.
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.
authors.affiliation: Centre for Cancer Biology, SA Pathology and University of South Australia, Frome Road, Adelaide, 5000, Australia.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Discipline of Psychiatry, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Jaehne
authors.affiliation: Centre for Cancer Biology, SA Pathology and University of South Australia, Frome Road, Adelaide, 5000, Australia.
authors.forename: Zarina
authors.initials: Z
authors.lastname: Greenberg
authors.affiliation: Centre for Cancer Biology, SA Pathology and University of South Australia, Frome Road, Adelaide, 5000, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: McCarthy
authors.affiliation: Centre for Cancer Biology, SA Pathology and University of South Australia, Frome Road, Adelaide, 5000, Australia.
authors.forename: Eiman
authors.initials: E
authors.lastname: Saleh
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3010, Australia.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Parish
authors.affiliation: School of Medical Sciences, RMIT University, Bundoora, 3083, Australia.
authors.forename: Daria
authors.initials: D
authors.lastname: Camera
authors.affiliation: 1] Harry Perkins Institute of Medical Research, Perth, Australia [2] School of Medicine and Pharmacology, University of Western Australia, Crawley, 6009, Australia.
authors.forename: Julian
authors.initials: J
authors.lastname: Heng
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, Clayton, Australia.
authors.forename: Matilda
authors.initials: M
authors.lastname: Haas
authors.affiliation: Discipline of Psychiatry, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3010, Australia.
authors.forename: Udani
authors.initials: U
authors.lastname: Ratnayake
authors.affiliation: 1] The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3010, Australia [2] Australian Regenerative Medicine Institute, Monash University, Clayton, Australia.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
authors.affiliation: Centre for Cancer Biology, SA Pathology and University of South Australia, Frome Road, Adelaide, 5000, Australia.
authors.forename: Angel F
authors.initials: AF
authors.lastname: Lopez
authors.affiliation: Centre for Cancer Biology, SA Pathology and University of South Australia, Frome Road, Adelaide, 5000, Australia.
authors.forename: Hayley S
authors.initials: HS
authors.lastname: Ramshaw
authors.affiliation: Centre for Cancer Biology, SA Pathology and University of South Australia, Frome Road, Adelaide, 5000, Australia.
authors.forename: Quenten
authors.initials: Q
authors.lastname: Schwarz
mesh_terms: D048948:14-3-3 Proteins / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020547:Lateral Ventricles / Q000378:metabolism / Q000473:pathology; D008297:Male; D018782:Maze Learning; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000473:pathology*; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology*; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction; D065852:Spatial Memory
chemical_list: D048948:14-3-3 Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D004298:Dopamine