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 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.
['Papadopoulou|Aikaterini S|AS|', 'Serneels|Lutgarde|L|', 'Achsel|Tilmann|T|', 'Mandemakers|Wim|W|', 'Callaerts-Vegh|Zsuzsanna|Z|', 'Dooley|James|J|', 'Lau|Pierre|P|', 'Ayoubi|Torik|T|', 'Radaelli|Enrico|E|', 'Spinazzi|Marco|M|', 'Neumann|Melanie|M|', 'Hébert|Sébastien S|SS|', 'Silahtaroglu|Asli|A|', 'Liston|Adrian|A|', "D'Hooge|Rudi|R|", 'Glatzel|Markus|M|', 'De Strooper|Bart|B|']
D000818:Animals D001259:Ataxia D001522:Behavior, Animal D002531:Cerebellum D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D035683:MicroRNAs D009043:Motor Activity D011689:Purkinje Cells D051670:Shaw Potassium Channels
Ataxia Purkinje cells Cerebellum Dendrites Locomotor behavior Voltage gated potassium channel miR-29a/b-1 cluster knockout