title: Early start of progressive motor deficits in Line 61 α-synuclein transgenic mice.
abstract: Synucleinopathies such as Parkinson's disease or multiple system atrophy are characterized by Lewy bodies in distinct brain areas. These aggregates are mainly formed by α-synuclein inclusions, a protein crucial for synaptic functions in the healthy brain. Transgenic animal models of synucleinopathies are frequently based on over-expression of human wild type or mutated α-synuclein under the regulatory control of different promoters. A promising model is the Line 61 α-synuclein transgenic mouse that expresses the transgene under control of the Thy-1 promoter.
  
  
  
  Here, we show an extended characterization of this mouse model over age. To this end, we analyzed animals for the progression of human and mouse protein expression levels in different brain areas as well as motor and memory deficits. Our results show, that Line 61 mice exhibited an age dependent increase of α-synuclein protein levels in the hippocampus but not the striatum. While murine α-synuclein was also increased with age, it was lower expressed in Line 61 mice than in non-transgenic littermates. At the age of 9 months animals exhibited increased neuroinflammation. Furthermore, we found that Line 61 mice showed severe motor deficits as early as 1 month of age as assessed by the wire hanging and nest building tests. At later ages, initial motor deficits were validated with the RotaRod, pasta gnawing and beam walk tests. At 8 months of age animals exhibited emotional memory deficits as validated with the contextual fear conditioning test.
  
  
  
  In summary, our results strengthen and further expand our knowledge about the Line 61 mouse model, emphasizing this mouse model as a valuable in vivo tool to test new compounds directed against synucleinopathies.
authors.affiliation: QPS Austria GmbH, Parkring 12, 8074, Grambach, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Rabl
authors.affiliation: QPS Austria GmbH, Parkring 12, 8074, Grambach, Austria.|Institute of Zoology, Karl Franzens University, Graz, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Breitschaedel
authors.affiliation: QPS Austria GmbH, Parkring 12, 8074, Grambach, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Flunkert
authors.affiliation: QPS Austria GmbH, Parkring 12, 8074, Grambach, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Duller
authors.affiliation: QPS Austria GmbH, Parkring 12, 8074, Grambach, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Amschl
authors.affiliation: QPS Austria GmbH, Parkring 12, 8074, Grambach, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Neddens
authors.affiliation: QPS Austria GmbH, Parkring 12, 8074, Grambach, Austria.
authors.forename: V
authors.initials: V
authors.lastname: Niederkofler
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Institute of Zoology, Karl Franzens University, Graz, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Roemer
authors.affiliation: QPS Austria GmbH, Parkring 12, 8074, Grambach, Austria. birgit.hutter-paier@qps.com.
authors.forename: B
authors.initials: B
authors.lastname: Hutter-Paier
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004660:Encephalitis / Q000378:metabolism; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D002479:Inclusion Bodies / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D010300:Parkinson Disease / Q000378:metabolism* / Q000523:psychology*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Memory deficits; Motor deficits; Parkinson’s disease; Protein expression; Synucleinopathies; α-Synuclein