Dysregulation of Rho GTPases in the αPix/Arhgef6 mouse model of X-linked intellectual disability is paralleled by impaired structural and synaptic plasticity and cognitive deficits.

Ger J A Ramakers; David Wolfer; Georg Rosenberger; Kerstin Kuchenbecker; Hans-Jürgen Kreienkamp; Janine Prange-Kiel; Gabriele M. Rune; Karin Richter; Kristina Langnaese; Sophie Masneuf; Michael R Bösl; Klaus-Dieter Fischer; Harm J Krugers; Hans-Peter Lipp; Elly van Galen; Kerstin Kutsche

Dysregulation of Rho GTPases in the αPix/Arhgef6 mouse model of X-linked intellectual disability is paralleled by impaired structural and synaptic plasticity and cognitive deficits.

Standard

Dysregulation of Rho GTPases in the αPix/Arhgef6 mouse model of X-linked intellectual disability is paralleled by impaired structural and synaptic plasticity and cognitive deficits. / Ramakers, Ger J A; Wolfer, David; Rosenberger, Georg; Kuchenbecker, Kerstin; Kreienkamp, Hans-Jürgen; Prange-Kiel, Janine; Rune, Gabriele M.; Richter, Karin; Langnaese, Kristina; Masneuf, Sophie; Bösl, Michael R; Fischer, Klaus-Dieter; Krugers, Harm J; Lipp, Hans-Peter; van Galen, Elly; Kutsche, Kerstin.

In: HUM MOL GENET, Vol. 21, No. 2, 2, 2012, p. 268-286.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Ramakers, GJA, Wolfer, D, Rosenberger, G, Kuchenbecker, K, Kreienkamp, H-J, Prange-Kiel, J, Rune, GM, Richter, K, Langnaese, K, Masneuf, S, Bösl, MR, Fischer, K-D, Krugers, HJ, Lipp, H-P, van Galen, E & Kutsche, K 2012, 'Dysregulation of Rho GTPases in the αPix/Arhgef6 mouse model of X-linked intellectual disability is paralleled by impaired structural and synaptic plasticity and cognitive deficits.', HUM MOL GENET, vol. 21, no. 2, 2, pp. 268-286. <http://www.ncbi.nlm.nih.gov/pubmed/21989057?dopt=Citation>

APA

Ramakers, G. J. A., Wolfer, D., Rosenberger, G., Kuchenbecker, K., Kreienkamp, H-J., Prange-Kiel, J., Rune, G. M., Richter, K., Langnaese, K., Masneuf, S., Bösl, M. R., Fischer, K-D., Krugers, H. J., Lipp, H-P., van Galen, E., & Kutsche, K. (2012). Dysregulation of Rho GTPases in the αPix/Arhgef6 mouse model of X-linked intellectual disability is paralleled by impaired structural and synaptic plasticity and cognitive deficits. HUM MOL GENET, 21(2), 268-286. [2]. http://www.ncbi.nlm.nih.gov/pubmed/21989057?dopt=Citation

Vancouver

Ramakers GJA, Wolfer D, Rosenberger G, Kuchenbecker K, Kreienkamp H-J, Prange-Kiel J et al. Dysregulation of Rho GTPases in the αPix/Arhgef6 mouse model of X-linked intellectual disability is paralleled by impaired structural and synaptic plasticity and cognitive deficits. HUM MOL GENET. 2012;21(2):268-286. 2.

Bibtex

@article{22387c34cf5b49a3a3dd3b13fbfa556d,

title = "Dysregulation of Rho GTPases in the αPix/Arhgef6 mouse model of X-linked intellectual disability is paralleled by impaired structural and synaptic plasticity and cognitive deficits.",

abstract = "Mutations in the ARHGEF6 gene, encoding the guanine nucleotide exchange factor ?PIX/Cool-2 for the Rho GTPases Rac1 and Cdc42, cause X-linked intellectual disability (ID) in humans. We show here that ?Pix/Arhgef6 is primarily expressed in neuropil regions of the hippocampus. To study the role of ?Pix/Arhgef6 in neuronal development and plasticity and gain insight into the pathogenic mechanisms underlying ID, we generated ?Pix/Arhgef6-deficient mice. Gross brain structure in these mice appeared to be normal; however, analysis of Golgi-Cox-stained pyramidal neurons revealed an increase in both dendritic length and spine density in the hippocampus, accompanied by an overall loss in spine synapses. Early-phase long-term potentiation was reduced and long-term depression was increased in the CA1 hippocampal area of ?Pix/Arhgef6-deficient animals. Knockout animals exhibited impaired spatial and complex learning and less behavioral control in mildly stressful situations, suggesting that this model mimics the human ID phenotype. The structural and electrophysiological alterations in the hippocampus were accompanied by a significant reduction in active Rac1 and Cdc42, but not RhoA. In conclusion, we suggest that imbalance in activity of different Rho GTPases may underlie altered neuronal connectivity and impaired synaptic function and cognition in ?Pix/Arhgef6 knockout mice.",

keywords = "Animals, Mice, Mice, Knockout, rho GTP-Binding Proteins/*metabolism, Maze Learning, *Disease Models, Animal, Neuronal Plasticity/*genetics, Cognition Disorders/*genetics, Genetic Diseases, X-Linked/*genetics, Guanine Nucleotide Exchange Factors/*genetics, Intellectual Disability/*genetics, Animals, Mice, Mice, Knockout, rho GTP-Binding Proteins/*metabolism, Maze Learning, *Disease Models, Animal, Neuronal Plasticity/*genetics, Cognition Disorders/*genetics, Genetic Diseases, X-Linked/*genetics, Guanine Nucleotide Exchange Factors/*genetics, Intellectual Disability/*genetics",

author = "Ramakers, {Ger J A} and David Wolfer and Georg Rosenberger and Kerstin Kuchenbecker and Hans-J{\"u}rgen Kreienkamp and Janine Prange-Kiel and Rune, {Gabriele M.} and Karin Richter and Kristina Langnaese and Sophie Masneuf and B{\"o}sl, {Michael R} and Klaus-Dieter Fischer and Krugers, {Harm J} and Hans-Peter Lipp and {van Galen}, Elly and Kerstin Kutsche",

year = "2012",

language = "English",

volume = "21",

pages = "268--286",

journal = "HUM MOL GENET",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "2",

}

RIS

TY - JOUR

T1 - Dysregulation of Rho GTPases in the αPix/Arhgef6 mouse model of X-linked intellectual disability is paralleled by impaired structural and synaptic plasticity and cognitive deficits.

AU - Ramakers, Ger J A

AU - Wolfer, David

AU - Rosenberger, Georg

AU - Kuchenbecker, Kerstin

AU - Kreienkamp, Hans-Jürgen

AU - Prange-Kiel, Janine

AU - Rune, Gabriele M.

AU - Richter, Karin

AU - Langnaese, Kristina

AU - Masneuf, Sophie

AU - Bösl, Michael R

AU - Fischer, Klaus-Dieter

AU - Krugers, Harm J

AU - Lipp, Hans-Peter

AU - van Galen, Elly

AU - Kutsche, Kerstin

PY - 2012

Y1 - 2012

N2 - Mutations in the ARHGEF6 gene, encoding the guanine nucleotide exchange factor ?PIX/Cool-2 for the Rho GTPases Rac1 and Cdc42, cause X-linked intellectual disability (ID) in humans. We show here that ?Pix/Arhgef6 is primarily expressed in neuropil regions of the hippocampus. To study the role of ?Pix/Arhgef6 in neuronal development and plasticity and gain insight into the pathogenic mechanisms underlying ID, we generated ?Pix/Arhgef6-deficient mice. Gross brain structure in these mice appeared to be normal; however, analysis of Golgi-Cox-stained pyramidal neurons revealed an increase in both dendritic length and spine density in the hippocampus, accompanied by an overall loss in spine synapses. Early-phase long-term potentiation was reduced and long-term depression was increased in the CA1 hippocampal area of ?Pix/Arhgef6-deficient animals. Knockout animals exhibited impaired spatial and complex learning and less behavioral control in mildly stressful situations, suggesting that this model mimics the human ID phenotype. The structural and electrophysiological alterations in the hippocampus were accompanied by a significant reduction in active Rac1 and Cdc42, but not RhoA. In conclusion, we suggest that imbalance in activity of different Rho GTPases may underlie altered neuronal connectivity and impaired synaptic function and cognition in ?Pix/Arhgef6 knockout mice.

AB - Mutations in the ARHGEF6 gene, encoding the guanine nucleotide exchange factor ?PIX/Cool-2 for the Rho GTPases Rac1 and Cdc42, cause X-linked intellectual disability (ID) in humans. We show here that ?Pix/Arhgef6 is primarily expressed in neuropil regions of the hippocampus. To study the role of ?Pix/Arhgef6 in neuronal development and plasticity and gain insight into the pathogenic mechanisms underlying ID, we generated ?Pix/Arhgef6-deficient mice. Gross brain structure in these mice appeared to be normal; however, analysis of Golgi-Cox-stained pyramidal neurons revealed an increase in both dendritic length and spine density in the hippocampus, accompanied by an overall loss in spine synapses. Early-phase long-term potentiation was reduced and long-term depression was increased in the CA1 hippocampal area of ?Pix/Arhgef6-deficient animals. Knockout animals exhibited impaired spatial and complex learning and less behavioral control in mildly stressful situations, suggesting that this model mimics the human ID phenotype. The structural and electrophysiological alterations in the hippocampus were accompanied by a significant reduction in active Rac1 and Cdc42, but not RhoA. In conclusion, we suggest that imbalance in activity of different Rho GTPases may underlie altered neuronal connectivity and impaired synaptic function and cognition in ?Pix/Arhgef6 knockout mice.

KW - Animals

KW - Mice

KW - Mice, Knockout

KW - rho GTP-Binding Proteins/metabolism

KW - Maze Learning

KW - Disease Models, Animal

KW - Neuronal Plasticity/genetics

KW - Cognition Disorders/genetics

KW - Genetic Diseases, X-Linked/genetics

KW - Guanine Nucleotide Exchange Factors/genetics

KW - Intellectual Disability/genetics

KW - Animals

KW - Mice

KW - Mice, Knockout

KW - rho GTP-Binding Proteins/metabolism

KW - Maze Learning

KW - Disease Models, Animal

KW - Neuronal Plasticity/genetics

KW - Cognition Disorders/genetics

KW - Genetic Diseases, X-Linked/genetics

KW - Guanine Nucleotide Exchange Factors/genetics

KW - Intellectual Disability/genetics

M3 - SCORING: Journal article

VL - 21

SP - 268

EP - 286

JO - HUM MOL GENET

JF - HUM MOL GENET

SN - 0964-6906

IS - 2

M1 - 2

ER -