Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice

Hongsheng Zhang; Eunchai Kang; Yaqing Wang; Chaojuan Yang; Hui Yu; Qin Wang; Zheyu Chen; Chen Zhang; Kimberly M. Christian; Hongjun Song; Guo Li Ming; Zhiheng Xu

doi:10.1038/ncomms11773

Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice

Hongsheng Zhang, Eunchai Kang, Yaqing Wang, Chaojuan Yang, Hui Yu, Qin Wang, Zheyu Chen, Chen Zhang, Kimberly M. Christian, Hongjun Song, Guo Li Ming^*, Zhiheng Xu

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

98 Citations (Scopus)

3 Downloads (Pure)

Abstract

Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

Original language	English
Article number	11773
Number of pages	12
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11773
Publication status	Published - 1 Jun 2016
Externally published	Yes

Bibliographical note

Acknowledgements: This work was supported by grants from NSF (31430037/31271156/ 31270826) and MOST (2014CB942801/2012CB517904/2012YQ03026006) to Z.X.; from NIH (NS048271, MH105128) to G.-l.M., from NIH (NS047344) to H.S., and from NRASAD to E.K. and K.M.C.

Author notes: Hongsheng Zhang, Eunchai Kang and Yaqing Wang: These authors contributed equally to this work.

Keywords

genetics of the nervous system
mutation
neurodevelopmental disorders
psychiatric disorders

Access to Document

10.1038/ncomms11773Licence: CC BY

Zhang_etal_NC_Brain_specific_VOR
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Final published version, 2.07 MBLicence: CC BY

Cite this

@article{0b5df2c0a58345c29c099d5ea3d48373,

title = "Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice",

abstract = "Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.",

keywords = "genetics of the nervous system, mutation, neurodevelopmental disorders, psychiatric disorders",

author = "Hongsheng Zhang and Eunchai Kang and Yaqing Wang and Chaojuan Yang and Hui Yu and Qin Wang and Zheyu Chen and Chen Zhang and Christian, {Kimberly M.} and Hongjun Song and Ming, {Guo Li} and Zhiheng Xu",

note = "Acknowledgements: This work was supported by grants from NSF (31430037/31271156/ 31270826) and MOST (2014CB942801/2012CB517904/2012YQ03026006) to Z.X.; from NIH (NS048271, MH105128) to G.-l.M., from NIH (NS047344) to H.S., and from NRASAD to E.K. and K.M.C. Author notes: Hongsheng Zhang, Eunchai Kang and Yaqing Wang: These authors contributed equally to this work.",

year = "2016",

month = jun,

day = "1",

doi = "10.1038/ncomms11773",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice

AU - Zhang, Hongsheng

AU - Kang, Eunchai

AU - Wang, Yaqing

AU - Yang, Chaojuan

AU - Yu, Hui

AU - Wang, Qin

AU - Chen, Zheyu

AU - Zhang, Chen

AU - Christian, Kimberly M.

AU - Song, Hongjun

AU - Ming, Guo Li

AU - Xu, Zhiheng

N1 - Acknowledgements: This work was supported by grants from NSF (31430037/31271156/ 31270826) and MOST (2014CB942801/2012CB517904/2012YQ03026006) to Z.X.; from NIH (NS048271, MH105128) to G.-l.M., from NIH (NS047344) to H.S., and from NRASAD to E.K. and K.M.C. Author notes: Hongsheng Zhang, Eunchai Kang and Yaqing Wang: These authors contributed equally to this work.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

AB - Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

KW - genetics of the nervous system

KW - mutation

KW - neurodevelopmental disorders

KW - psychiatric disorders

UR - http://www.scopus.com/inward/record.url?scp=84973387079&partnerID=8YFLogxK

U2 - 10.1038/ncomms11773

DO - 10.1038/ncomms11773

M3 - Article

C2 - 27249678

AN - SCOPUS:84973387079

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11773

ER -

Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Eunchai Kang

Cite this

Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Profiles

Eunchai Kang

Cite this