A NOVEL HUMAN HETEROZYGOUS STAT5B VARIANT LEADS TO GROWTH AND DEVELOPMENTAL DEFECTS IN ZEBRAFISH EMBRYOS

LILIANA KARABATAS; PAULA SCAGLIA; NORA SANGUINETI; PAOLA PLAZAS; LAURA RAMIREZ; ANA CLAUDIA KESELMAN; IGNACIO BERGADA; SABINA DOMENE; ESTEFANIA LANDI; MARIANA GUTIERREZ; DEBORA BRASLAVSKY; HECTOR GUILLERMO JASPER

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Sociedad Argentina de Investigacion Clinica

Abstract/Resumen: Signal transducer and activator oftranscription 5B (STAT5B) has been identified as a keydownstream mediator of Growth Hormone (GH) signaling insomatic growth. Autosomic recessive human mutations inSTAT5B lead to severe growth retardation associated to immunedysregulation. On the other hand, some heterozygous STAT5Bmutations have been associated to a milder form of the disease.The aim of our study was to evaluate the functionalconsequences of a novel heterozygous human STAT5B variant(K632N), described in a child presenting short stature with mildimmunological dysfunction, during zebrafish embryodevelopment to determine its pathogenicity. To do this, wemicroinjected 100 and 200 pg of wildtype (WT) and mutantmRNA into zebrafish embryos and measured the embryo lengthat 72 hours post fertilization (hpf). In addition, we characterizedthe morphological phenotypes observed in these embryos.Zebrafish embryos microinyected with 100 and 200 pg of mutantmRNA show a dose dependent significant reduction of bodylength at 72 hpf compared to those microinyected with the samedose of WT mRNA (p