Xenopus as a Model for GI/Pancreas Disease

Abstract

Diseases affecting endodermal organs like the pancreas, lung and gastrointestinal (GI) tract have a substantial impact on human welfare. Since many of these are congenital defects that arise as a result of defects during development broad efforts are focused on understanding the development of these organs so as to better identify risk factors, disease mechanisms and therapeutic targets. Studies implementing model systems, like the amphibian Xenopus, have contributed immensely to our understanding of signaling (e.g. Wnt, FGF, BMP, RA) pathways and gene regulation (e.g. hhex, ptf1a, ngn3) that underlie normal development as well as disease progression. Recent advances in genome engineering further enhance the capabilities of the Xenopus model system for pursuing biomedical research, and will undoubtedly result in a boom of new information underlying disease mechanisms ultimately leading to advancements in diagnosis and therapy.

Using Xenopus to understand human disease and developmental disorders

“…The use of Xenopus eggs and embryos for in vivo analyses of disease gene expression and function has exploded in recent years. This model has supported important advances in our understanding of: neurological disorders including autism, Alzheimer's disease, and depression (James et al, ; Park et al, ; Ramirez‐Vizcarrando, Hasan, Gu, Khakhalin, & Aizenman, ; Ullah, Demuro, Parker, & Pearson, ); cancers (Green, Kwon, & Christian, ; Haynes‐Gilmore et al, ; Van Nieuwenhuysen et al, ; Wei et al, ); congenital heart defects (Endicott, Basu, Khokha, & Brueckner, ; Silva et al, ; Torres‐Prioris, Smith, Mohun, Fernández, & Durán, ); craniofacial and auditory malformations (Dickinson, ; Griffin, Sondalle, Del Viso, Baserga, & Khokha, ; Moody, Neilson, Kenyon, Alfandari, & Pignoni, ; Ramírez‐Gordillo et al, ); diabetes (Kofent & Spagnoli, ; Pearl, Jarikji, & Horb, ; Salanga & Horb, ); kidney disease (Desgrange & Cereghini, ; Lienkamp, ; Stiburkova, Stekrova, Nakamura, & Ichida, ); Lennox–Gastaut syndrome (Hammer, Ebert, Jensen, & Jensen, ); and Zimmermann–Laband syndrome (Kortüm et al, ).…”

An update on genetically engineered mouse models of pancreatic neuroendocrine neoplasms

“…other rodents, zebrafish, Xenopus frogs, and organoids). For instance, zebrafish lines evolved considerably during the last decade and are now being used in many preclinical settings in PanNETs and PanNECs (Vitale et al 2014, Gaudenzi et al 2020; Xenopus tropicalis frogs were also recently endorsed as PanNEC models (Naert et al 2020); both are useful models to study the NE system (Salanga & Horb 2015, McNamara et al 2018, Gaudenzi et al 2020. Patientderived xenografts (PDXs) provide a relevant, specific drug screening application capacity in a more personalized approach.…”

Xenbase: Facilitating the Use of Xenopus to Model Human Disease

“…Finally, researchers use Xenopus embryos and tadpoles to model a broad range of human diseases from cardiovascular to mental health disorders. Experimental advantages include the large abundant externally developing embryos and transparent skin of later tadpoles, allowing one to examine organ development and disease, such as those occurring in the foregut, kidney, heart and brain (Salanga and Horb, 2015; Lienkamp, 2016; Dubey and Saint-Jeannet, 2017; Garfinkel and Khokha, 2017; Sater and Moody, 2017; Blum and Ott, 2018). Candidate human disease-causing genes are commonly studied by overexpression or knockdown of the orthologous Xenopus gene and analyzing the resulting phenotype, which if it resembles the human condition, can be used to study the details of pathogenesis or even provide a platform for therapeutics.…”