Producción CyT
Congreso
Autoría
Recalcatti Macarena
;
Braccalenti Michela
;
Salatino Lucía
;
Fernandez María Celia
;
MARTIN, AYELEN
;
Domené, Horacio
;
Pennisi Patricia
;
Plazas Paola
;
Domené, Sabina
Fecha
2025
Editorial y Lugar de Edición
Fundación Revista Medicina
Resumen
Información suministrada por el agente en
SIGEVA
The insulin-like growth factor 1 (IGF1) is highly conserved among vertebrates and plays a central role in pre- and postnatal growth. IGF1 deficiency due to homozygous pathogenic variants in IGF1 gene leads to intrauterine and postnatal delay of growth often associated with deafness and mental retardation. Our objective was to develop a functional assay to determine the pathogenicity of two humans variants in IGF1found in patients with severe growth retardation using the zebrafish model. While t...
The insulin-like growth factor 1 (IGF1) is highly conserved among vertebrates and plays a central role in pre- and postnatal growth. IGF1 deficiency due to homozygous pathogenic variants in IGF1 gene leads to intrauterine and postnatal delay of growth often associated with deafness and mental retardation. Our objective was to develop a functional assay to determine the pathogenicity of two humans variants in IGF1found in patients with severe growth retardation using the zebrafish model. While the patient with p.Ser35Cys has normal hearing and cognitive development close to normal, the patient with p.Tyr60His has mental retardation and deafness. We performed overexpression assays using WT IGF1mRNA and variants, microinjecting them into zebrafish embryos followed by phenotype scoring. Overexpression of WT IGF1 mRNA resulted in embryos with cyclopia (37%), pericardial edema (52%), yolk edema (54%), and tail malformation (43%). Conversely, overexpression of variants p.Ser35Cys and p.Tyr60Hisresulted in embryos with significantly less malformations(p<0.05), pericardial edema (7%; 0%), yolk edema (17%;5%), and tail malformation (10%; 0%) respectively. Cartilage development was evaluated using Alcian Blue. Overexpression of WT IGF1 mRNA led to a significant decrease in cartilage length compared to uninfected embryos. Interestingly, overexpression of p.Tyr60His variant did not affect cartilage length while p.Ser35Cys led to a shortening similar to that obtained with WT IGF1.In conclusion, our study suggests that the pathogenic nature of p.Tyr60His is due to a lack of function, whilep.Ser35Cys retained minimal biological activity. This assay will allow the study of future IGF1 variants.
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Palabras Clave
IGF1Zebrafish