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.

Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson-disease gene / I. Guella, A. Pistocchi, R. Asselta, V. Rimoldi, A. Ghilardi, F. Sironi, L. Trotta, P. Primignani, M. Zini, A. Zecchinelli, D. Coviello, G. Pezzoli, L. Del Giacco, S. Duga, S. Goldwurm. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - 32:11(2011 Nov), pp. 1994-2005.

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

I. Guella
Primo
;
A. Pistocchi
Secondo
;
R. Asselta;A. Ghilardi;L. Del Giacco;S. Duga
Penultimo
;
2011

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.
GIGYF2; Morpholino oligonucleotide; MPP+; Mutational screening; PARK11; Parkinson disease; Zebrafish
Settore BIO/06 - Anatomia Comparata e Citologia
Settore BIO/11 - Biologia Molecolare
nov-2011
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/209852
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