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Transgenic modeling of Ndr2 gene amplification reveals disturbance of hippocampus circuitry and function

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Transgenic modeling of Ndr2 gene amplification reveals disturbance of hippocampus circuitry and function. / Madencioglu, Deniz A; Çalışkan, Gürsel; Yuanxiang, Pingan; Rehberg, Kati; Demiray, Yunus E; Kul, Emre; Engler, Alexander; Hayani, Hussam; Bergado-Acosta, Jorge R; Kummer, Anne; Müller, Iris; Song, Inseon; Dityatev, Alexander; Kähne, Thilo; Kreutz, Michael R; Stork, Oliver.

in: ISCIENCE, Jahrgang 24, Nr. 8, 20.08.2021, S. 102868.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Madencioglu, DA, Çalışkan, G, Yuanxiang, P, Rehberg, K, Demiray, YE, Kul, E, Engler, A, Hayani, H, Bergado-Acosta, JR, Kummer, A, Müller, I, Song, I, Dityatev, A, Kähne, T, Kreutz, MR & Stork, O 2021, 'Transgenic modeling of Ndr2 gene amplification reveals disturbance of hippocampus circuitry and function', ISCIENCE, Jg. 24, Nr. 8, S. 102868. https://doi.org/10.1016/j.isci.2021.102868

APA

Madencioglu, D. A., Çalışkan, G., Yuanxiang, P., Rehberg, K., Demiray, Y. E., Kul, E., Engler, A., Hayani, H., Bergado-Acosta, J. R., Kummer, A., Müller, I., Song, I., Dityatev, A., Kähne, T., Kreutz, M. R., & Stork, O. (2021). Transgenic modeling of Ndr2 gene amplification reveals disturbance of hippocampus circuitry and function. ISCIENCE, 24(8), 102868. https://doi.org/10.1016/j.isci.2021.102868

Vancouver

Madencioglu DA, Çalışkan G, Yuanxiang P, Rehberg K, Demiray YE, Kul E et al. Transgenic modeling of Ndr2 gene amplification reveals disturbance of hippocampus circuitry and function. ISCIENCE. 2021 Aug 20;24(8):102868. https://doi.org/10.1016/j.isci.2021.102868

Bibtex

@article{ff50c95bae4141a5af95fae355e123f0,
title = "Transgenic modeling of Ndr2 gene amplification reveals disturbance of hippocampus circuitry and function",
abstract = "Duplications and deletions of short chromosomal fragments are increasingly recognized as the cause for rare neurodevelopmental conditions and disorders. The NDR2 gene encodes a protein kinase important for neuronal development and is part of a microduplication region on chromosome 12 that is associated with intellectual disabilities, autism, and epilepsy. We developed a conditional transgenic mouse with increased Ndr2 expression in postmigratory forebrain neurons to study the consequences of an increased gene dosage of this Hippo pathway kinase on brain circuitry and cognitive functions. Our analysis reveals reduced terminal fields and synaptic transmission of hippocampal mossy fibers, altered hippocampal network activity, and deficits in mossy fiber-dependent behaviors. Reduced doublecortin expression and protein interactome analysis indicate that transgenic Ndr2 disturbs the maturation of granule cells in the dentate gyrus. Together, our data suggest that increased expression of Ndr2 may critically contribute to the development of intellectual disabilities upon gene amplification.",
author = "Madencioglu, {Deniz A} and G{\"u}rsel {\c C}alı{\c s}kan and Pingan Yuanxiang and Kati Rehberg and Demiray, {Yunus E} and Emre Kul and Alexander Engler and Hussam Hayani and Bergado-Acosta, {Jorge R} and Anne Kummer and Iris M{\"u}ller and Inseon Song and Alexander Dityatev and Thilo K{\"a}hne and Kreutz, {Michael R} and Oliver Stork",
note = "{\textcopyright} 2021 The Author(s).",
year = "2021",
month = aug,
day = "20",
doi = "10.1016/j.isci.2021.102868",
language = "English",
volume = "24",
pages = "102868",
journal = "ISCIENCE",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "8",

}

RIS

TY - JOUR

T1 - Transgenic modeling of Ndr2 gene amplification reveals disturbance of hippocampus circuitry and function

AU - Madencioglu, Deniz A

AU - Çalışkan, Gürsel

AU - Yuanxiang, Pingan

AU - Rehberg, Kati

AU - Demiray, Yunus E

AU - Kul, Emre

AU - Engler, Alexander

AU - Hayani, Hussam

AU - Bergado-Acosta, Jorge R

AU - Kummer, Anne

AU - Müller, Iris

AU - Song, Inseon

AU - Dityatev, Alexander

AU - Kähne, Thilo

AU - Kreutz, Michael R

AU - Stork, Oliver

N1 - © 2021 The Author(s).

PY - 2021/8/20

Y1 - 2021/8/20

N2 - Duplications and deletions of short chromosomal fragments are increasingly recognized as the cause for rare neurodevelopmental conditions and disorders. The NDR2 gene encodes a protein kinase important for neuronal development and is part of a microduplication region on chromosome 12 that is associated with intellectual disabilities, autism, and epilepsy. We developed a conditional transgenic mouse with increased Ndr2 expression in postmigratory forebrain neurons to study the consequences of an increased gene dosage of this Hippo pathway kinase on brain circuitry and cognitive functions. Our analysis reveals reduced terminal fields and synaptic transmission of hippocampal mossy fibers, altered hippocampal network activity, and deficits in mossy fiber-dependent behaviors. Reduced doublecortin expression and protein interactome analysis indicate that transgenic Ndr2 disturbs the maturation of granule cells in the dentate gyrus. Together, our data suggest that increased expression of Ndr2 may critically contribute to the development of intellectual disabilities upon gene amplification.

AB - Duplications and deletions of short chromosomal fragments are increasingly recognized as the cause for rare neurodevelopmental conditions and disorders. The NDR2 gene encodes a protein kinase important for neuronal development and is part of a microduplication region on chromosome 12 that is associated with intellectual disabilities, autism, and epilepsy. We developed a conditional transgenic mouse with increased Ndr2 expression in postmigratory forebrain neurons to study the consequences of an increased gene dosage of this Hippo pathway kinase on brain circuitry and cognitive functions. Our analysis reveals reduced terminal fields and synaptic transmission of hippocampal mossy fibers, altered hippocampal network activity, and deficits in mossy fiber-dependent behaviors. Reduced doublecortin expression and protein interactome analysis indicate that transgenic Ndr2 disturbs the maturation of granule cells in the dentate gyrus. Together, our data suggest that increased expression of Ndr2 may critically contribute to the development of intellectual disabilities upon gene amplification.

U2 - 10.1016/j.isci.2021.102868

DO - 10.1016/j.isci.2021.102868

M3 - SCORING: Journal article

C2 - 34381982

VL - 24

SP - 102868

JO - ISCIENCE

JF - ISCIENCE

SN - 2589-0042

IS - 8

ER -