Is Zebrafish a Good Model for the Alpha-Gal Syndrome?

The alpha-Gal syndrome (AGS) is an underdiagnosed tick-borne allergy characterized by both immediate and delayed IgE-mediated anaphylactic reactions to the galactose-alpha-1,3-galactose (alpha-Gal) epitope. Common manifestations include gastrointestinal, cutaneous, and respiratory symptoms appearing 2-6 h after the consumption of mammalian meat or derived products. Zebrafish (Danio rerio) are emerging as essential animal models in biomedical studies, due to their anatomical, genetic, and physiological similarities to humans, with significant applications in toxicology, behavioral research, oncology, and inflammation studies. The mechanisms associated with AGS are sustained by studies in the humanized α1,3GalT-KO C57BL/6 mouse (Mus musculus) and zebrafish animal models for the production of anti-alpha-Gal antibodies in response to tick saliva, the development of allergic reactions in animals sensitized with tick protein extracts following mammalian meat consumption, and the identification of immune mechanisms. The immune mechanisms characterized in both models are associated with a skewed type 2 immune response, triggering Toll-Like receptor (TLR) signaling pathways, IL-4 production, and humoral activity. These results support the use of both models rather than a single one for a more comprehensive characterization of AGS-associated immune mechanisms. In this study, we focused on the use of zebrafish as a model for biomedicine research in immunity, infectious, and allergic diseases, with a particular emphasis on the AGS and the identification of candidate therapeutic interventions. Based on insights from multiple studies, we concluded that zebrafish is a suitable model for studying the AGS, considering the addressed limitations and in combination with the α1,3GalT-KO mouse model.