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

doi:10.1016/j.nbd.2014.10.006

. 2015 Jan:73:275-88.

doi: 10.1016/j.nbd.2014.10.006. Epub 2014 Oct 12.

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

Aikaterini S Papadopoulou¹, Lutgarde Serneels¹, Tilmann Achsel¹, Wim Mandemakers², Zsuzsanna Callaerts-Vegh³, James Dooley⁴, Pierre Lau¹, Torik Ayoubi⁵, Enrico Radaelli¹, Marco Spinazzi¹, Melanie Neumann⁶, Sébastien S Hébert⁷, Asli Silahtaroglu⁸, Adrian Liston⁴, Rudi D'Hooge⁹, Markus Glatzel⁴, Bart De Strooper¹⁰

Affiliations

¹ VIB 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.
² Department of Clinical genetics, Erasmus MC Faculty Building, 3015GE Rotterdam, The Netherlands.
³ Laboratory of Biological Psychology, Department of Psychology, University of Leuven, 3000 Leuven, Belgium.
⁴ Autoimmune Genetics Laboratory, Department of Microbiology and Immunology, VIB and KULeuven, 3000 Leuven, Belgium.
⁵ VIB 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 Netherlands.
⁶ Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, UKE, 20246 Hamburg, Germany.
⁷ Centre de Recherche du CHUQ de Quebec, CHUL, Axe Neurosciences, Quebec, Canada; Université Laval, Département de psychiatrie et de neurosciences, G1V 4G2 Quebec, Canada.
⁸ Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Kobenhavn, Denmark.
⁹ Center 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, Belgium.
¹⁰ VIB 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. Electronic address: Bart.DeStrooper@cme.vib-kuleuven.be.

PMID: 25315682
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 et al. Neurobiol Dis. 2015 Jan.

. 2015 Jan:73:275-88.

doi: 10.1016/j.nbd.2014.10.006. Epub 2014 Oct 12.

Authors

Affiliations

¹ VIB 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.
² Department of Clinical genetics, Erasmus MC Faculty Building, 3015GE Rotterdam, The Netherlands.
³ Laboratory of Biological Psychology, Department of Psychology, University of Leuven, 3000 Leuven, Belgium.
⁴ Autoimmune Genetics Laboratory, Department of Microbiology and Immunology, VIB and KULeuven, 3000 Leuven, Belgium.
⁵ VIB 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 Netherlands.
⁶ Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, UKE, 20246 Hamburg, Germany.
⁷ Centre de Recherche du CHUQ de Quebec, CHUL, Axe Neurosciences, Quebec, Canada; Université Laval, Département de psychiatrie et de neurosciences, G1V 4G2 Quebec, Canada.
⁸ Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Kobenhavn, Denmark.
⁹ Center 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, Belgium.
¹⁰ VIB 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. Electronic address: Bart.DeStrooper@cme.vib-kuleuven.be.

PMID: 25315682
DOI: 10.1016/j.nbd.2014.10.006

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.

Keywords: Ataxia; Cerebellum; Dendrites; Locomotor behavior; Purkinje cells; Voltage gated potassium channel; miR-29a/b-1 cluster knockout.

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

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

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