14-3-3{zeta} 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 Ik-Tsen Heng, Matilda Ann Haas, Bernhard T Baune, Udani Ratnayake, Maarten van den Buuse, Angel F Lopez, Hayley S Ramshaw, Quenten P Schwarz

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14 Citations (Scopus)

Abstract

Sequencing and expression analyses implicate 14-3-3 zeta as a genetic risk factor for neurodevelopmental disorders such as schizophrenia and autism. In support of this notion, we recently found that 14-3-3 zeta (-/-) 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 14-3-3 zeta (-/-) phenotype. In addition to replicating defects such as aberrant mossy fibre connectivity and impaired spatial memory, our analysis of 14-3-3 zeta (-/-) 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, 14-3-3 zeta (-/-) 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 14-3-3 zeta gives rise to many of the pathological hallmarks associated with the human condition. 14-3-3 zeta -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)1 - 15
Number of pages15
JournalScientific Reports
Volume5
Issue number(Art. No:12434)
DOIs
Publication statusPublished - 2015

Cite this

Xu, X., Jaehne, E. J., Greenberg, Z., McCarthy, P., Saleh, E., Parish, C. L., ... Schwarz, Q. P. (2015). 14-3-3{zeta} deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders. Scientific Reports, 5((Art. No:12434)), 1 - 15. https://doi.org/10.1038/srep12434
Xu, Xiangjun ; Jaehne, Emily J ; Greenberg, Zarina ; McCarthy, Peter ; Saleh, Eiman ; Parish, Clare L ; Camera, Daria ; Heng, Julian Ik-Tsen ; Haas, Matilda Ann ; Baune, Bernhard T ; Ratnayake, Udani ; van den Buuse, Maarten ; Lopez, Angel F ; Ramshaw, Hayley S ; Schwarz, Quenten P. / 14-3-3{zeta} deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders. In: Scientific Reports. 2015 ; Vol. 5, No. (Art. No:12434). pp. 1 - 15.
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title = "14-3-3{zeta} deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders",
abstract = "Sequencing and expression analyses implicate 14-3-3 zeta as a genetic risk factor for neurodevelopmental disorders such as schizophrenia and autism. In support of this notion, we recently found that 14-3-3 zeta (-/-) 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 14-3-3 zeta (-/-) phenotype. In addition to replicating defects such as aberrant mossy fibre connectivity and impaired spatial memory, our analysis of 14-3-3 zeta (-/-) 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, 14-3-3 zeta (-/-) 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 14-3-3 zeta gives rise to many of the pathological hallmarks associated with the human condition. 14-3-3 zeta -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.",
author = "Xiangjun Xu and Jaehne, {Emily J} and Zarina Greenberg and Peter McCarthy and Eiman Saleh and Parish, {Clare L} and Daria Camera and Heng, {Julian Ik-Tsen} and Haas, {Matilda Ann} and Baune, {Bernhard T} and Udani Ratnayake and {van den Buuse}, Maarten and Lopez, {Angel F} and Ramshaw, {Hayley S} and Schwarz, {Quenten P}",
year = "2015",
doi = "10.1038/srep12434",
language = "English",
volume = "5",
pages = "1 -- 15",
journal = "Scientific Reports",
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Xu, X, Jaehne, EJ, Greenberg, Z, McCarthy, P, Saleh, E, Parish, CL, Camera, D, Heng, JI-T, Haas, MA, Baune, BT, Ratnayake, U, van den Buuse, M, Lopez, AF, Ramshaw, HS & Schwarz, QP 2015, '14-3-3{zeta} deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders', Scientific Reports, vol. 5, no. (Art. No:12434), pp. 1 - 15. https://doi.org/10.1038/srep12434

14-3-3{zeta} 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 Ik-Tsen; Haas, Matilda Ann; Baune, Bernhard T; Ratnayake, Udani; van den Buuse, Maarten; Lopez, Angel F; Ramshaw, Hayley S; Schwarz, Quenten P.

In: Scientific Reports, Vol. 5, No. (Art. No:12434), 2015, p. 1 - 15.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - 14-3-3{zeta} 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 Ik-Tsen

AU - Haas, Matilda Ann

AU - Baune, Bernhard T

AU - Ratnayake, Udani

AU - van den Buuse, Maarten

AU - Lopez, Angel F

AU - Ramshaw, Hayley S

AU - Schwarz, Quenten P

PY - 2015

Y1 - 2015

N2 - Sequencing and expression analyses implicate 14-3-3 zeta as a genetic risk factor for neurodevelopmental disorders such as schizophrenia and autism. In support of this notion, we recently found that 14-3-3 zeta (-/-) 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 14-3-3 zeta (-/-) phenotype. In addition to replicating defects such as aberrant mossy fibre connectivity and impaired spatial memory, our analysis of 14-3-3 zeta (-/-) 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, 14-3-3 zeta (-/-) 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 14-3-3 zeta gives rise to many of the pathological hallmarks associated with the human condition. 14-3-3 zeta -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 14-3-3 zeta as a genetic risk factor for neurodevelopmental disorders such as schizophrenia and autism. In support of this notion, we recently found that 14-3-3 zeta (-/-) 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 14-3-3 zeta (-/-) phenotype. In addition to replicating defects such as aberrant mossy fibre connectivity and impaired spatial memory, our analysis of 14-3-3 zeta (-/-) 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, 14-3-3 zeta (-/-) 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 14-3-3 zeta gives rise to many of the pathological hallmarks associated with the human condition. 14-3-3 zeta -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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513550/pdf/srep12434.pdf

U2 - 10.1038/srep12434

DO - 10.1038/srep12434

M3 - Article

VL - 5

SP - 1

EP - 15

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - (Art. No:12434)

ER -