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

Aikaterini S Papadopoulou; Lutgarde Serneels; Tilmann Achsel; Wim Mandemakers; Zsuzsanna Callaerts-Vegh; James Dooley; Pierre Lau; Torik Ayoubi; Enrico Radaelli; Marco Spinazzi; Melanie Neumann; Sébastien S Hébert; Asli Silahtaroglu; Adrian Liston; Rudi D'Hooge; Markus Glatzel; Bart 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

Aikaterini S Papadopoulou, Lutgarde Serneels, Tilmann Achsel, Wim Mandemakers, Zsuzsanna Callaerts-Vegh, James Dooley, Pierre Lau, Torik Ayoubi, Enrico Radaelli, Marco Spinazzi, Melanie Neumann, Sébastien S Hébert, Asli Silahtaroglu, Adrian Liston, Rudi D'Hooge, Markus Glatzel, Bart De Strooper

Medical Genetics Program

37 Citationer (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 KCNC3 expression may contribute to the ataxic phenotype.

Originalsprog	Engelsk
Tidsskrift	Neurobiology of Disease
Vol/bind	73
Sider (fra-til)	275-288
Antal sider	14
ISSN	0969-9961
DOI	https://doi.org/10.1016/j.nbd.2014.10.006
Status	Udgivet - 1 jan. 2015

Adgang til dokumentet

10.1016/j.nbd.2014.10.006

Citationsformater

Papadopoulou, A. S., Serneels, L., Achsel, T., Mandemakers, W., Callaerts-Vegh, Z., Dooley, J., Lau, P., Ayoubi, T., Radaelli, E., Spinazzi, M., Neumann, M., Hébert, S. S., 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

Papadopoulou, AS, Serneels, L, Achsel, T, Mandemakers, W, Callaerts-Vegh, Z, Dooley, J, Lau, P, Ayoubi, T, Radaelli, E, Spinazzi, M, Neumann, M, Hébert, 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, bind 73, s. 275-288. https://doi.org/10.1016/j.nbd.2014.10.006

@article{585e5da1447f451ab5609e1aa6eb99be,

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 KCNC3 expression may contribute to the ataxic phenotype.",

author = "Papadopoulou, {Aikaterini S} and Lutgarde Serneels and Tilmann Achsel and Wim Mandemakers and Zsuzsanna Callaerts-Vegh and James Dooley and Pierre Lau and Torik Ayoubi and Enrico Radaelli and Marco Spinazzi and Melanie Neumann and H{\'e}bert, {S{\'e}bastien S} and Asli Silahtaroglu and Adrian Liston and Rudi D'Hooge and Markus Glatzel and {De Strooper}, Bart",

note = "Copyright {\textcopyright} 2014. Published by Elsevier Inc.",

year = "2015",

month = jan,

day = "1",

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

language = "English",

volume = "73",

pages = "275--288",

journal = "Neurobiology of Disease",

issn = "0969-9961",

publisher = "Academic Press",

}

TY - JOUR

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

AU - Papadopoulou, Aikaterini S

AU - Serneels, Lutgarde

AU - Achsel, Tilmann

AU - Mandemakers, Wim

AU - Callaerts-Vegh, Zsuzsanna

AU - Dooley, James

AU - Lau, Pierre

AU - Ayoubi, Torik

AU - Radaelli, Enrico

AU - Spinazzi, Marco

AU - Neumann, Melanie

AU - Hébert, Sébastien S

AU - Silahtaroglu, Asli

AU - Liston, Adrian

AU - D'Hooge, Rudi

AU - Glatzel, Markus

AU - De Strooper, Bart

PY - 2015/1/1

Y1 - 2015/1/1

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 KCNC3 expression may contribute to the ataxic phenotype.

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 KCNC3 expression may contribute to the ataxic phenotype.

U2 - 10.1016/j.nbd.2014.10.006

DO - 10.1016/j.nbd.2014.10.006

M3 - Journal article

C2 - 25315682

SN - 0969-9961

VL - 73

SP - 275

EP - 288

JO - Neurobiology of Disease

JF - Neurobiology of Disease

ER -

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

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater