Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson-disease gene

Ilaria Guella, Anna Pistocchi, Rosanna Asselta, Valeria Rimoldi, Anna Ghilardi, Francesca Sironi, Luca Trotta, Paola Primignani, Michela Zini, Anna Zecchinelli, Domenico Coviello, Gianni Pezzoli, Luca Del Giacco, Stefano Duga, Stefano Goldwurm

Research output: Contribution to journalArticle

Abstract

The Grb10-Interacting GYF Protein-2 (GIGYF2) gene has been proposed as the Parkinson-disease (PD) gene underlying the PARK11 locus. However, association of GIGYF2 with PD has been challenged and a functional validation of GIGYF2 mutations is lacking.In this frame, we performed a mutational screening of GIGYF2 in an Italian PD cohort. Exons containing known mutations were analyzed in 552 cases and 552 controls. Thereafter, a subset of 184 familial PD cases and controls were subjected to a full coding-exon screening. These analyses identified 8 missense variations in 9 individuals (4 cases, 5 controls).Furthermore, we developed a zebrafish model of gigyf2 deficiency. Abrogation of gigyf2 function in zebrafish embryos did not lead to a drastic cell loss in diencephalic dopaminergic (DA) neuron clusters, suggesting that gigyf2 is not required for DA neuron differentiation. Notably, gigyf2 functional abrogation did not increase diencephalic DA neurons susceptibility to the PD-inducing drug MPP+.These data, together with those recently reported by other groups, suggest that GIGYF2 is unlikely to be the PARK11 gene.

Original languageEnglish
Pages (from-to)1994-2005
Number of pages12
JournalNeurobiology of Aging
Volume32
Issue number11
DOIs
Publication statusPublished - Nov 2011

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Keywords

  • GIGYF2
  • Morpholino oligonucleotide
  • MPP+
  • Mutational screening
  • PARK11
  • Parkinson disease
  • Zebrafish

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Guella, I., Pistocchi, A., Asselta, R., Rimoldi, V., Ghilardi, A., Sironi, F., Trotta, L., Primignani, P., Zini, M., Zecchinelli, A., Coviello, D., Pezzoli, G., Del Giacco, L., Duga, S., & Goldwurm, S. (2011). Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson-disease gene. Neurobiology of Aging, 32(11), 1994-2005. https://doi.org/10.1016/j.neurobiolaging.2009.12.016