Identification of multiple QTLs linked to neuropathology in the engrailed-1 heterozygous mouse model of Parkinson's disease

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Motor symptoms in Parkinson's disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro-striatal axons in the SwissOF1-En1+/- mouse strain. In contrast, C57Bl/6-En1+/- mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD-like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/- and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/- 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson's disease-like damage in rodent disease models and considered in clinical association studies in PD.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Umeå University
  • Cleveland Clinic
  • Lund University
  • Van Andel Research Institute
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper
Originalspråkengelska
Artikelnummer31701
TidskriftScientific Reports
Volym6
StatusPublished - 2016 aug 23
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Itzia Jimenez, 2019, Lund: Lund University, Faculty of Medicine. 113 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Maria Swanberg & Konnova, E. A., 2018 dec 21, Parkinson's Disease: Pathogenesis and Clinical Aspects. Stoker, T. B. & Greenland, J. C. (red.). Brisbane (AU): Codon Publications, s. 83-106

Forskningsoutput: Kapitel i bok/rapport/Conference proceedingKapitel samlingsverk

Jewett, M., 2017, Lund: Lund University, Faculty of Medicine. 87 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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