Abstract
Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the genetic basis of PWS, the mechanisms underlying the pathogenesis of the disorder remain poorly understood. Treatment for PWS consists mainly of palliative therapies; curative therapies are sorely needed. Zebrafish, Danio rerio, represent a promising way forward for elucidating physiological problems such as obesity and identifying new pharmacotherapeutic options for PWS. Over the last decade, an increased appreciation for the highly conserved biology among vertebrates and the ability to perform high-throughput drug screening has seen an explosion in the use of zebrafish for disease modeling and drug discovery. Here, we review recent advances in developing zebrafish models of human disease. Aspects of zebrafish genetics and physiology that are relevant to PWS will be discussed, and the advantages and disadvantages of zebrafish models will be contrasted with current animal models for this syndrome. Finally, we will present a paradigm for drug screening in zebrafish that is potentially the fastest route for identifying and delivering curative pharmacotherapies to PWS patients.
Highlights
Prader-Willi syndrome (PWS) is a complex neurogenetic disorder, which results in cognitive and neuroendocrine dysfunction
The majority of PWS-related genes are highly conserved in mammals so a number of mouse models are providing important insight into the genetic underpinnings of PWS
Examination of potentially orthologous genes in zebrafish indicates that the imprinted PWS region has newly arisen in the mammalian lineage, within a highly conserved cluster of non-imprinted neural related genes
Summary
Prader-Willi syndrome (PWS) is a complex neurogenetic disorder, which results in cognitive and neuroendocrine dysfunction. Individuals with PWS present a spectrum of clinically observed phenotypes. Between the ages of 4.5 and 8, children with PWS experience rapid onset of hyperphagia and obesity [1,2,3]. While behavioral therapy can mitigate weight gain, complications from obesity are the leading cause of morbidity in PWS [4]. Sleep-disordered breathing and daytime hypersomnolence are associated with PWS. PWS individuals are cognitively disabled, with an average IQ of 65 [1]. The disorder causes behavioral abnormalities such as skin picking and tantrums. Current treatment options for PWS consist of hormone administration and behavioral therapy (Table 1) [1,4,6,7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
