Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice

AS Papadopoulou; L Serneels; T Achsel; W Mandemakers; Z Callaerts-Vegh; J Dooley; P Lau; T Ayoubi; E Radaelli; M Spinazzi; M (Manuela) Neumann; SS Hebert; A Silahtaroglu; A Liston; R D'Hooge; M Glatzel; B De Strooper

doi:10.1016/j.nbd.2014.10.006

Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice

AS Papadopoulou, L Serneels, T Achsel, W Mandemakers, Z Callaerts-Vegh, J Dooley, P Lau, T Ayoubi, E Radaelli, M Spinazzi, M (Manuela) Neumann, SS Hebert, A Silahtaroglu, A Liston, R D'Hooge, M Glatzel, B De Strooper

Obstetrics & Gynecology

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44 Citations (Scopus)

Abstract

miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia. The different members of the miR-29 family are strongly expressed in neurons of the olfactory bulb, the hippocampus and in the Purkinje cells of the cerebellum. Morphological analysis showed that Purkinje cells are smaller and display less dendritic arborisation compared to their wildtype littermates. In addition, a decreased number of parallel fibers form synapses on the Purkinje cells. We identified several mRNAs significantly up-regulated in the absence of the miR-29a/b-1 cluster. At the protein level, however, the voltage-gated potassium channel Kcnc3 (Kv3.3) was significantly up-regulated in the cerebella of the miR-29a/b knockout mice. Dysregulation of KCNO expression may contribute to the ataxic phenotype. (C) 2015 Elsevier Inc All rights reserved.

Original language	Undefined/Unknown
Pages (from-to)	275-288
Number of pages	14
Journal	Neurobiology of Disease
Volume	73
DOIs	https://doi.org/10.1016/j.nbd.2014.10.006
Publication status	Published - 2015

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10.1016/j.nbd.2014.10.006

http://hdl.handle.net/1765/84765

Cite this

Papadopoulou, AS., Serneels, L., Achsel, T., Mandemakers, W., Callaerts-Vegh, Z., Dooley, J., Lau, P., Ayoubi, T., Radaelli, E., Spinazzi, M., Neumann, M., Hebert, SS., Silahtaroglu, A., Liston, A., D'Hooge, R., Glatzel, M., & De Strooper, B. (2015). Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice. Neurobiology of Disease, 73, 275-288. https://doi.org/10.1016/j.nbd.2014.10.006

@article{366a6bfc80c4491ea182111d0d887945,

title = "Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice",

abstract = "miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia. The different members of the miR-29 family are strongly expressed in neurons of the olfactory bulb, the hippocampus and in the Purkinje cells of the cerebellum. Morphological analysis showed that Purkinje cells are smaller and display less dendritic arborisation compared to their wildtype littermates. In addition, a decreased number of parallel fibers form synapses on the Purkinje cells. We identified several mRNAs significantly up-regulated in the absence of the miR-29a/b-1 cluster. At the protein level, however, the voltage-gated potassium channel Kcnc3 (Kv3.3) was significantly up-regulated in the cerebella of the miR-29a/b knockout mice. Dysregulation of KCNO expression may contribute to the ataxic phenotype. (C) 2015 Elsevier Inc All rights reserved.",

author = "AS Papadopoulou and L Serneels and T Achsel and W Mandemakers and Z Callaerts-Vegh and J Dooley and P Lau and T Ayoubi and E Radaelli and M Spinazzi and Neumann, {M (Manuela)} and SS Hebert and A Silahtaroglu and A Liston and R D'Hooge and M Glatzel and {De Strooper}, B",

year = "2015",

doi = "10.1016/j.nbd.2014.10.006",

language = "Undefined/Unknown",

volume = "73",

pages = "275--288",

journal = "Neurobiology of Disease",

issn = "0969-9961",

publisher = "Academic Press",

}

Papadopoulou, AS, Serneels, L, Achsel, T, Mandemakers, W, Callaerts-Vegh, Z, Dooley, J, Lau, P, Ayoubi, T, Radaelli, E, Spinazzi, M, Neumann, M, Hebert, SS, Silahtaroglu, A, Liston, A, D'Hooge, R, Glatzel, M & De Strooper, B 2015, 'Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice', Neurobiology of Disease, vol. 73, pp. 275-288. https://doi.org/10.1016/j.nbd.2014.10.006

TY - JOUR

T1 - Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice

AU - Papadopoulou, AS

AU - Serneels, L

AU - Achsel, T

AU - Mandemakers, W

AU - Callaerts-Vegh, Z

AU - Dooley, J

AU - Lau, P

AU - Ayoubi, T

AU - Radaelli, E

AU - Spinazzi, M

AU - Neumann, M (Manuela)

AU - Hebert, SS

AU - Silahtaroglu, A

AU - Liston, A

AU - D'Hooge, R

AU - Glatzel, M

AU - De Strooper, B

PY - 2015

Y1 - 2015

N2 - miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia. The different members of the miR-29 family are strongly expressed in neurons of the olfactory bulb, the hippocampus and in the Purkinje cells of the cerebellum. Morphological analysis showed that Purkinje cells are smaller and display less dendritic arborisation compared to their wildtype littermates. In addition, a decreased number of parallel fibers form synapses on the Purkinje cells. We identified several mRNAs significantly up-regulated in the absence of the miR-29a/b-1 cluster. At the protein level, however, the voltage-gated potassium channel Kcnc3 (Kv3.3) was significantly up-regulated in the cerebella of the miR-29a/b knockout mice. Dysregulation of KCNO expression may contribute to the ataxic phenotype. (C) 2015 Elsevier Inc All rights reserved.

AB - miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia. The different members of the miR-29 family are strongly expressed in neurons of the olfactory bulb, the hippocampus and in the Purkinje cells of the cerebellum. Morphological analysis showed that Purkinje cells are smaller and display less dendritic arborisation compared to their wildtype littermates. In addition, a decreased number of parallel fibers form synapses on the Purkinje cells. We identified several mRNAs significantly up-regulated in the absence of the miR-29a/b-1 cluster. At the protein level, however, the voltage-gated potassium channel Kcnc3 (Kv3.3) was significantly up-regulated in the cerebella of the miR-29a/b knockout mice. Dysregulation of KCNO expression may contribute to the ataxic phenotype. (C) 2015 Elsevier Inc All rights reserved.

U2 - 10.1016/j.nbd.2014.10.006

DO - 10.1016/j.nbd.2014.10.006

M3 - Article

SN - 0969-9961

VL - 73

SP - 275

EP - 288

JO - Neurobiology of Disease

JF - Neurobiology of Disease

ER -