A G309D-Pink1 knock-in mouse model of the PARK6-form of Parkinson's disease

• Applicant: Dr. Suzana Gispert-Sánchez
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2005 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 18857684

• Final Report Year: 2009

Final Report Abstract

The G309D-Pinkl knock-in and a Pinkl knock-out (KO) mouse were generated. The KO mouse showed adult onset and progression of impaired spontaneous movement, together with brain mitochondrial and synaptic dysfunction in the absence of neurodegeneration. Murine embryonal fibroblasts did not show the typical features of PARK6 patient fibroblasts. The project results underline the relevance of Pinkl for mitochondrial bioenergetics.

Publications

• Abahuni N, Gispert S, Bauer P, Riess O, Krüger R, Becker T, Auburger G. Mitochondrial translation initiation factor 3 gene polymorphism associated with Parkinson's disease. Neurosci Lett. 2007 Mar 6;414(2): 126-9.
  
  
• Exner N, Treske B, Paquet D, Holmström K, Schiesling C, Gispert 5, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Krüger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C. Loss-of-function ofhuman PINKl results in mitochondrial pathology and can be rescued by parkin. J Neurosci. 2007 Nov 7:27f45):12413-8.
  
  
• Hoepken HH, Gispert 5, Morales B, Wingerter O, Del Turco D, Mülsch A, Nussbaum RL, Müller K, Dröse S, Brandt U, Deller T, Wirth B, Kudin AP, Kunz WS, Auburger G. Mitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6. Neurobiol Dis. 2007 Feb;25(2):401-ll. Epub 2006 Nov 30.
  
  
• Hoepken HH, Gispert S, Azizov M, Klinkenberg M, Ricciardi F, Kurz A, Morales-Gordo B, Bonin M, Riess O, Gasser T, Kögel D, Steinmetz H, Auburger G. Parkinson patient fibroblasts show increased alpha-synuclein expression. Exp Neurol. 2008 Aug;212(2):307- 13. Epub 2008 Apr 16.