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.
authors.affiliation: 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.
authors.forename: Aikaterini S
authors.initials: AS
authors.lastname: Papadopoulou
authors.affiliation: 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.
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Serneels
authors.affiliation: 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.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Achsel
authors.affiliation: Department of Clinical genetics, Erasmus MC Faculty Building, 3015GE Rotterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Mandemakers
authors.affiliation: Laboratory of Biological Psychology, Department of Psychology, University of Leuven, 3000 Leuven, Belgium.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Callaerts-Vegh
authors.affiliation: Autoimmune Genetics Laboratory, Department of Microbiology and Immunology, VIB and KULeuven, 3000 Leuven, Belgium.
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.affiliation: 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.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lau
authors.affiliation: 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.
authors.forename: Torik
authors.initials: T
authors.lastname: Ayoubi
authors.affiliation: 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.
authors.forename: Enrico
authors.initials: E
authors.lastname: Radaelli
authors.affiliation: 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.
authors.forename: Marco
authors.initials: M
authors.lastname: Spinazzi
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, UKE, 20246 Hamburg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Neumann
authors.affiliation: Centre de Recherche du CHUQ de Quebec, CHUL, Axe Neurosciences, Quebec, Canada; Université Laval, Département de psychiatrie et de neurosciences, G1V 4G2 Quebec, Canada.
authors.forename: Sébastien S
authors.initials: SS
authors.lastname: Hébert
authors.affiliation: 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.
authors.forename: Asli
authors.initials: A
authors.lastname: Silahtaroglu
authors.affiliation: Autoimmune Genetics Laboratory, Department of Microbiology and Immunology, VIB and KULeuven, 3000 Leuven, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
authors.affiliation: 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.
authors.forename: Rudi
authors.initials: R
authors.lastname: D'Hooge
authors.affiliation: Autoimmune Genetics Laboratory, Department of Microbiology and Immunology, VIB and KULeuven, 3000 Leuven, Belgium.
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.affiliation: 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.
authors.forename: Bart
authors.initials: B
authors.lastname: De Strooper
mesh_terms: D000818:Animals; D001259:Ataxia / Q000378:metabolism*; D001522:Behavior, Animal; D002531:Cerebellum / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D009043:Motor Activity; D011689:Purkinje Cells / Q000378:metabolism*; D051670:Shaw Potassium Channels / Q000378:metabolism*
chemical_list: C085724:Kcnc3 protein, mouse; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D051670:Shaw Potassium Channels
keywords: Ataxia; Cerebellum; Dendrites; Locomotor behavior; Purkinje cells; Voltage gated potassium channel; miR-29a/b-1 cluster knockout