Zebrafish as a Model Organism for TTC37-Related Trichohepatoenteric Syndrome: Genetic Models and Phenotypic Aspects

This study aimed to characterize a ttc37 knockout zebrafish model as an in vivo system for investigating TTC37-related THES. The mutant line was validated through PCR-based genotyping and agarose gel electrophoresis, allowing the identification of wild-type, heterozygous, and homozygous animals. Bioinformatic analyses were performed to characterize the zebrafish ttc37 gene, its predicted Ttc37 protein structure, conserved TPR domains, and protein–protein interaction network within the SKI-exosome pathway. Single-cell transcriptomic data were also analyzed to evaluate ttc37 expression in cell populations relevant to THES pathology. In vivo reporter imaging was used to assess selected functional features of the model. The Tg(mpx:GFP) reporter enabled visualization of neutrophil distribution, while the Tg(lipan:mCherry) reporter allowed evaluation of lipid- associated signal in the digestive/hepatic region. Overall, this study supports the ttc37 knockout zebrafish as a genetically and biologically relevant model for TTC37-related THES and provides a basis for future mechanistic and therapeutic investigations.