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Glasl, L. ; Kloos, K. ; Giesert, F. ; Roethig, A. ; di Benedetto, B.* ; Kühn, R. ; Zhang, J. ; Hafen, U. ; Zerle, J. ; Hofmann, A. ; Hrabě de Angelis, M. ; Winklhofer, K.F.* ; Hölter, S.M. ; Vogt Weisenhorn, D.M. ; Wurst, W.

Pink1-deficiency in mice impairs gait, olfaction and serotonergic innervation of the olfactory bulb.

Exp. Neurol. 235, 214-227 (2012)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Parkinson's Disease (PD) is the most common neurodegenerative movement disorder. Autosomal-recessive mutations in the mitochondrial protein kinase PINK1 (PTEN-induced kinase 1) account for 1-2% of the hereditary early-onset cases. To study the mechanisms underlying disease development, we generated Pink1-deficient mice. In analogy to other genetic loss-of-function mouse models, Pink1(-/-) mice did not show morphological alterations in the dopaminergic system. As a consequence, no gross motor dysfunctions were observed indicating that these mice do not develop the cardinal symptoms of PD. Nonetheless, symptoms which develop mainly before bradykinesia, rigidity and resting tremor were clearly evident in Pink1-deficient mice. These symptoms were gait alterations and olfactory dysfunctions. Remarkably in the glomerular layer of the olfactory bulb the density of serotonergic fibers was significantly reduced. Concerning mitochondrial morphology, neurons in Pink1(-/-) mice had less fragmented mitochondria. In contrast, upon acute knock-down of Pink1 increased mitochondrial fragmentation was observed in neuronal cultures. This fragmentation was, however, evened out within days. Taken together, we demonstrate that Pink1-deficient mice exhibit behavioral symptoms of early phases of PD and present systematic experimental evidence for compensation of Pink1-deficiency at the cellular level. Thus, Pink1-deficient mice represent a model for the early phases of PD in which compensation may still impede the onset of neurodegeneration. Consequently, these mice are a valuable tool for studying Pink1-related PD development, as well as for searching for reliable PD biomarkers.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Early-onset Parkinson's Disease; Genetic mouse model; Compensation; Mitochondrial dysfunction; Olfactory dysfunction; Gait impairment
Sprache
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 0014-4886
e-ISSN 1090-2430
Zeitschrift Experimental Neurology
Quellenangaben Band: 235, Heft: 1, Seiten: 214-227 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort San Diego, Calif.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
POF Topic(s) 30204 - Cell Programming and Repair
30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500500-001
G-500600-003
G-500500-003
PubMed ID 22265660
DOI 10.1016/j.expneurol.2012.01.002
WOS ID WOS:000303430400023
Scopus ID 84862777779
Erfassungsdatum 2012-03-23
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