Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice
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 i...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-01-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999611400299X |
| id |
doaj-4cfe1d691b9748729b660c08f5ce439c |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice Neurobiology of Disease miR-29a/b-1 cluster knockout Ataxia Locomotor behavior Cerebellum Purkinje cells Dendrites |
| author_facet |
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 |
| author_sort |
Aikaterini S. Papadopoulou |
| title |
Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice |
| title_short |
Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice |
| title_full |
Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice |
| title_fullStr |
Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice |
| title_full_unstemmed |
Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice |
| title_sort |
deficiency of the mir-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice |
| publisher |
Elsevier |
| series |
Neurobiology of Disease |
| issn |
1095-953X |
| publishDate |
2015-01-01 |
| description |
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. |
| topic |
miR-29a/b-1 cluster knockout Ataxia Locomotor behavior Cerebellum Purkinje cells Dendrites |
| url |
http://www.sciencedirect.com/science/article/pii/S096999611400299X |
| work_keys_str_mv |
AT aikaterinispapadopoulou deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT lutgardeserneels deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT tilmannachsel deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT wimmandemakers deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT zsuzsannacallaertsvegh deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT jamesdooley deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT pierrelau deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT torikayoubi deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT enricoradaelli deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT marcospinazzi deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT melanieneumann deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT sebastienshebert deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT aslisilahtaroglu deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT adrianliston deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT rudidhooge deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT markusglatzel deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice AT bartdestrooper deficiencyofthemir29ab1clusterleadstoataxicfeaturesandcerebellaralterationsinmice |
| _version_ |
1724208224176963584 |
| spelling |
doaj-4cfe1d691b9748729b660c08f5ce439c2021-03-22T12:42:01ZengElsevierNeurobiology of Disease1095-953X2015-01-0173275288Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in miceAikaterini S. Papadopoulou0Lutgarde Serneels1Tilmann Achsel2Wim Mandemakers3Zsuzsanna Callaerts-Vegh4James Dooley5Pierre Lau6Torik Ayoubi7Enrico Radaelli8Marco Spinazzi9Melanie Neumann10Sébastien S. Hébert11Asli Silahtaroglu12Adrian Liston13Rudi D'Hooge14Markus Glatzel15Bart De Strooper16VIB Center for the Biology of Disease, VIB Leuven 3000 Leuven, Belgium; Center for Human Genetics and Leuven institute for neurodegenerative disorders (LIND), KU Leuven and Universitaire Ziekenhuizen, 3000 Leuven, BelgiumVIB Center for the Biology of Disease, VIB Leuven 3000 Leuven, Belgium; Center for Human Genetics and Leuven institute for neurodegenerative disorders (LIND), KU Leuven and Universitaire Ziekenhuizen, 3000 Leuven, BelgiumVIB Center for the Biology of Disease, VIB Leuven 3000 Leuven, Belgium; Center for Human Genetics and Leuven institute for neurodegenerative disorders (LIND), KU Leuven and Universitaire Ziekenhuizen, 3000 Leuven, BelgiumDepartment of Clinical genetics, Erasmus MC Faculty Building, 3015GE Rotterdam, The NetherlandsLaboratory of Biological Psychology, Department of Psychology, University of Leuven, 3000 Leuven, BelgiumAutoimmune Genetics Laboratory, Department of Microbiology and Immunology, VIB and KULeuven, 3000 Leuven, BelgiumVIB Center for the Biology of Disease, VIB Leuven 3000 Leuven, Belgium; Center for Human Genetics and Leuven institute for neurodegenerative disorders (LIND), KU Leuven and Universitaire Ziekenhuizen, 3000 Leuven, BelgiumVIB Center for the Biology of Disease, VIB Leuven 3000 Leuven, Belgium; Center for Human Genetics and Leuven institute for neurodegenerative disorders (LIND), KU Leuven and Universitaire Ziekenhuizen, 3000 Leuven, Belgium; Saint James School of Medicine, Plaza Juliana, Kralendijk, Bonaire, Dutch Caribbean, The NetherlandsVIB Center for the Biology of Disease, VIB Leuven 3000 Leuven, Belgium; Center for Human Genetics and Leuven institute for neurodegenerative disorders (LIND), KU Leuven and Universitaire Ziekenhuizen, 3000 Leuven, BelgiumVIB Center for the Biology of Disease, VIB Leuven 3000 Leuven, Belgium; Center for Human Genetics and Leuven institute for neurodegenerative disorders (LIND), KU Leuven and Universitaire Ziekenhuizen, 3000 Leuven, BelgiumInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, UKE, 20246 Hamburg, GermanyCentre de Recherche du CHUQ de Quebec, CHUL, Axe Neurosciences, Quebec, Canada; Université Laval, Département de psychiatrie et de neurosciences, G1V 4G2 Quebec, CanadaWilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Kobenhavn, DenmarkAutoimmune Genetics Laboratory, Department of Microbiology and Immunology, VIB and KULeuven, 3000 Leuven, BelgiumCenter for Human Genetics and Leuven institute for neurodegenerative disorders (LIND), KU Leuven and Universitaire Ziekenhuizen, 3000 Leuven, Belgium; Laboratory of Biological Psychology, Department of Psychology, University of Leuven, 3000 Leuven, BelgiumAutoimmune Genetics Laboratory, Department of Microbiology and Immunology, VIB and KULeuven, 3000 Leuven, BelgiumVIB Center for the Biology of Disease, VIB Leuven 3000 Leuven, Belgium; Center for Human Genetics and Leuven institute for neurodegenerative disorders (LIND), KU Leuven and Universitaire Ziekenhuizen, 3000 Leuven, Belgium; Department of Molecular Neuroscience, UCL Institute of Neurology, WC1N 3BG London, UK; Corresponding author at: Laboratory for the Research of Neurodegenerative Diseases, VIB Center for the Biology of Disease, KU Leuven Center for Human Genetics, O&N4 Herestraat 49 box 602, 3000 Leuven, Belgium.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.http://www.sciencedirect.com/science/article/pii/S096999611400299XmiR-29a/b-1 cluster knockoutAtaxiaLocomotor behaviorCerebellumPurkinje cellsDendrites |