Think Small: Zebrafish as a Model System of Human Pathology

Table 1

Zebrafish gastrointestinal models of pathology.

Model	Mechanism of pathology	Human relevancy/key features	Key references
Pan-GI neoplasias	Heterozygotic APC mutation	APC mutations drive spontaneous and genetic intestinal adenocarcinomas.	Haramis et al., 2006 [24]
Hepatocellular carcinoma	Thioacetamide ± HCV-core-protein-zebrafish	Human genetic overlap. Rising prevalence of HCV-driven HCC in humans.	Lam and Gong, 2006 [25]; Rekha et al., 2008 [26]
Pancreatic cancer	Transgenic ptf1a-KRAS zebrafish	Recapitulates hedgehog signaling aberrations found in humans. Elucidates a potential cellular origin for pancreatic cancers.	Park et al., 2008 [27]
Inflammatory bowel disease	TNBS in the media of zebrafish larvae	Model inflammatory and goblet cell hypertrophy. Responds to bacterial status and IBD medications.	Flemming et al., 2010 [28]; Oehlers et al., 2011 [29]
Inflammatory bowel disease	Oxazolone enema in adult zebrafish	Goblet cell depletion and eosinophil infiltration. Responds to antibiotic therapy.	Brugman et al., 2009 [30]
NAFLD	Mutation in a novel gene: foigr^hi1532b.; Alternative model involves chemical induction with thioacetamide	Large lipid filled hepatocytes and cellular apoptosis; pathology linked to ER stress responses. Alternative model generates a fatty liver and hepatocyte apoptosis.	Cinaroglu et al., 2011 [31]; Amali et al., 2006 [32] (alternative model)
Alcoholic liver disease	2% ethanol to the water of 4 dpf zebrafish for 32 days	Hepatomegaly and steatosis, with upregulation of genes involved in toxic alcohol metabolism. Model is sensitive to sterol regulatory binding protein, important in human disease.	Passeri et al., 2009 [33]

Abbreviations: GI: gastrointestinal; APC: adenomatous polyposis coli; HCV: hepatitis C virus; TNBS: 2,4,6-trinitrobenzene sulfonic acid; IBD: inflammatory bowel diseases; NAFLD: nonalcoholic fatty liver disease; ER: endoplasmic reticulum.