title: Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration.
abstract: Zinc finger motifs are distributed amongst many eukaryotic protein families, directing nucleic acid-protein and protein-protein interactions. Zinc finger protein 106 (ZFP106) has previously been associated with roles in immune response, muscle differentiation, testes development and DNA damage, although little is known about its specific function. To further investigate the function of ZFP106, we performed an in-depth characterization of Zfp106 deficient mice (Zfp106(-/-)), and we report a novel role for ZFP106 in motor and sensory neuronal maintenance and survival. Zfp106(-/-) mice develop severe motor abnormalities, major deficits in muscle strength and histopathological changes in muscle. Intriguingly, despite being highly expressed throughout the central nervous system, Zfp106(-/-) mice undergo selective motor and sensory neuronal and axonal degeneration specific to the spinal cord and peripheral nervous system. Neurodegeneration does not occur during development of Zfp106(-/-) mice, suggesting that ZFP106 is likely required for the maintenance of mature peripheral motor and sensory neurons. Analysis of embryonic Zfp106(-/-) motor neurons revealed deficits in mitochondrial function, with an inhibition of Complex I within the mitochondrial electron transport chain. Our results highlight a vital role for ZFP106 in sensory and motor neuron maintenance and reveal a novel player in mitochondrial dysfunction and neurodegeneration.
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: Peter I
authors.initials: PI
authors.lastname: Joyce
authors.affiliation: UCL Institute of Neurology and MRC Centre for Neuromuscular Disease, Queen Square, London WC1N 3BG, UK.
authors.forename: Pietro
authors.initials: P
authors.lastname: Fratta
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: Allison S
authors.initials: AS
authors.lastname: Landman
authors.affiliation: UCL Institute of Neurology and MRC Centre for Neuromuscular Disease, Queen Square, London WC1N 3BG, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Mcgoldrick
authors.affiliation: Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: Henning
authors.initials: H
authors.lastname: Wackerhage
authors.affiliation: UCL Institute of Neurology and MRC Centre for Neuromuscular Disease, Queen Square, London WC1N 3BG, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Groves
authors.affiliation: Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: Bharani Shiva
authors.initials: BS
authors.lastname: Busam
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Jorge
authors.initials: J
authors.lastname: Galino
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: Silvia
authors.initials: S
authors.lastname: Corrochano
authors.affiliation: UCL Institute of Neurology and MRC Centre for Neuromuscular Disease, Queen Square, London WC1N 3BG, UK.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Beskina
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Esapa
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Ryder
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Carter
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Stewart
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: Codner
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Hilton
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: Lydia
authors.initials: L
authors.lastname: Teboul
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tucker
authors.affiliation: Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: Arimantas
authors.initials: A
authors.lastname: Lionikas
authors.affiliation: Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK and.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Estabel
authors.affiliation: Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK and.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Ramirez-Solis
authors.affiliation: Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK and.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: White
authors.affiliation: UCL Institute of Neurology and MRC Centre for Neuromuscular Disease, Queen Square, London WC1N 3BG, UK.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
authors.affiliation: UCL Genetics Institute, London WC1E 6BT, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: David L H
authors.initials: DL
authors.lastname: Bennet
authors.affiliation: UCL Institute of Neurology and MRC Centre for Neuromuscular Disease, Queen Square, London WC1N 3BG, UK.
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Abramov
authors.affiliation: UCL Institute of Neurology and MRC Centre for Neuromuscular Disease, Queen Square, London WC1N 3BG, UK, a.acevedo@har.mrc.ac.uk e.fisher@prion.ucl.ac.uk l.greensmith@ucl.ac.uk.
authors.forename: Linda
authors.initials: L
authors.lastname: Greensmith
authors.affiliation: UCL Institute of Neurology and MRC Centre for Neuromuscular Disease, Queen Square, London WC1N 3BG, UK, a.acevedo@har.mrc.ac.uk e.fisher@prion.ucl.ac.uk l.greensmith@ucl.ac.uk.
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Fisher
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK, a.acevedo@har.mrc.ac.uk e.fisher@prion.ucl.ac.uk l.greensmith@ucl.ac.uk.
authors.forename: Abraham
authors.initials: A
authors.lastname: Acevedo-Arozena
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D009046:Motor Neurons / Q000378:metabolism* / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C116200:Zfp106 protein, mouse