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.

LanguageEnglish
Pages12434
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

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 ; van den Buuse, Maarten ; Lopez, Angel F ; Ramshaw, Hayley S ; Schwarz, Quenten. / 14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders. In: Scientific Reports. 2015 ; Vol. 5. pp. 12434.
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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.",
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author = "Xiangjun Xu and Jaehne, {Emily J} and Zarina Greenberg and Peter McCarthy and Eiman Saleh and Parish, {Clare L} and Daria Camera and Julian Heng and Matilda Haas and Baune, {Bernhard T} and Udani Ratnayake and {van den Buuse}, Maarten and Lopez, {Angel F} and Ramshaw, {Hayley S} and Quenten Schwarz",
year = "2015",
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Xu, X, Jaehne, EJ, Greenberg, Z, McCarthy, P, Saleh, E, Parish, CL, Camera, D, Heng, J, Haas, M, Baune, BT, Ratnayake, U, van den Buuse, M, Lopez, AF, Ramshaw, HS & Schwarz, Q 2015, '14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders', Scientific Reports, vol. 5, pp. 12434. https://doi.org/10.1038/srep12434

14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders. / 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; van den Buuse, Maarten; Lopez, Angel F; Ramshaw, Hayley S; Schwarz, Quenten.

In: Scientific Reports, Vol. 5, 24.07.2015, p. 12434.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 14-3-3ζ deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders

AU - Xu, Xiangjun

AU - Jaehne, Emily J

AU - Greenberg, Zarina

AU - McCarthy, Peter

AU - Saleh, Eiman

AU - Parish, Clare L

AU - Camera, Daria

AU - Heng, Julian

AU - Haas, Matilda

AU - Baune, Bernhard T

AU - Ratnayake, Udani

AU - van den Buuse, Maarten

AU - Lopez, Angel F

AU - Ramshaw, Hayley S

AU - Schwarz, Quenten

PY - 2015/7/24

Y1 - 2015/7/24

N2 - 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.

AB - 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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KW - Animals

KW - Disease Models, Animal

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KW - Gene Expression

KW - Lateral Ventricles

KW - Male

KW - Maze Learning

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Knockout

KW - Mossy Fibers, Hippocampal

KW - Pyramidal Cells

KW - Schizophrenia

KW - Signal Transduction

KW - Spatial Memory

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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