TY - JOUR
T1 - Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson-disease gene
AU - Guella, Ilaria
AU - Pistocchi, Anna
AU - Asselta, Rosanna
AU - Rimoldi, Valeria
AU - Ghilardi, Anna
AU - Sironi, Francesca
AU - Trotta, Luca
AU - Primignani, Paola
AU - Zini, Michela
AU - Zecchinelli, Anna
AU - Coviello, Domenico
AU - Pezzoli, Gianni
AU - Del Giacco, Luca
AU - Duga, Stefano
AU - Goldwurm, Stefano
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - GIGYF2
KW - Morpholino oligonucleotide
KW - MPP+
KW - Mutational screening
KW - PARK11
KW - Parkinson disease
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=80052613693&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052613693&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2009.12.016
DO - 10.1016/j.neurobiolaging.2009.12.016
M3 - Article
C2 - 20060621
AN - SCOPUS:80052613693
VL - 32
SP - 1994
EP - 2005
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 11
ER -