Overexpression of Cnbp rescues morphant phenotype in zebrafish model of Treacher Collins Syndrome (TCS)

PORCEL DE PERALTA, MAURO S.; MOUGUELAR, VALERIA S.; CARNEVALE, MATIAS; COUX, GABRIELA; CALCATERRA, NORA B

Mar del Plata

Congreso; 51st Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2015

SAIB

TCS is a mandibulofacial dysostosis due to mutations in TCOF1 in which patients show variable expressivity inphenotype. Recent studies suggest that genetic background contribute to these clinical variations. Among the proteinsinvolved in craniofacial development that are affected in the pathology is CNBP (cellular nucleic acid bindingprotein). We developed an alternative to the murine model of the disease by injecting zebrafish embryos withmorpholinos against the TCOF1 ortholog (nolc1). The purpose of this study was: a) to validate zebrafish TCS-likemodel with respect to the murine model of the syndrome; b) to study the link between Nolc1 and Cnbp. In TCS-likezebrafish embryos we found, in agreement with the reported findings in Tcof1+/- mouse, a reduction of pre-RNAr47S levels, Tp53 stabilization and an induction of apoptosis markers. Besides, we evaluated the effect of differentCnbp abundance (using fish lines with high and low over-expression of cnbp) on the expression of nolc1 and thecraniofacial phenotype of TCS-like embryos. Our findings suggest that Cnbp acts as a transcriptional activatorof nolc1 and its over-expression rescues cranial cartilage defects. In conclusion, the TCS-like model in zebrafishreplicates the results described in Tcof1+/- mouse. More importantly, embryonic basal levels of Cnbp should play asignificant role in TCS expressivity.