hrp0082fc4.2 | Growth | ESPE2014

The Effect of grB10-Deficiency in Zebrafish: A Translational Animal Model to Study Human Growth

De Leonibus Chiara , Barinaga-Rementeria Ramirez Irene , Hurlstone Adam , Clayton Peter , Stevens Adam

Background: GRB10 negatively regulates IGF1 signalling, influences growth and promoter polymorphisms are associated with GH response1. GRB10 knockout-mouse models display foetal overgrowth2, however, the mouse model has only partial similarity to human growth3. There is evidence that the zebrafish is an appropriate model to study growth4 and has the advantage of being easily genetically manipulated.<p class="abs...

hrp0084p2-401 | GH &amp; IGF | ESPE2015

GRB10 Knockdown in Zebrafish is Associated with Decreased Weight-to-length Ratio without Alterations in AKT and ERK Activity: A Model to Study Human Growth Regulation

De Leonibus Chiara , Broadbent Jack , Murray Philip , Whitehead Joseph , Hurlstone Adam , Shiels Holly , Clayton Peter , Stevens Adam

Background: In humans GRB10 negatively regulates GH and IGF1 signaling predominantly via altering phosphorylation of PI3K/mTOR/AKT and MEK/ERK pathways which relate to both growth and metabolic function. We have previously shown that Grb10 knockdown in Zebrafish results in overgrowth with an increase in length and head size. However the impact on weight in relation to length has not been assessed.Objective: To develop a model t...

hrp0097p1-480 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2023

Grb10a Knockdown in Early Life Permanently Alters Growth, Cardiometabolic Phenotype, and the Co-ordination of the Whole Transcriptome in Zebrafish

Evans Bridget , Garner Terence , De Leonibus Chiara , Wearing Oliver , Shiels Holly , Hurlstone Adam , Clayton Peter , Stevens Adam

The ‘Developmental Origins of Health and Disease’ (DOHaD) hypothesis encapsulates the relationship between pre- and perinatal exposures causing altered growth and the development of later life disease. Mediators of this relationship have not been fully defined. We have used zebrafish [ZF] (Danio rerio) as a potential model for DOHaD, modifying expression of grb10a, an adapter protein that interacts with the insulin and IGF receptors, to act as a negative r...