Genetically-modified zebrafish lacking one or more immune-related genes, and the use thereof, e.g., in cell or tissue transplantation methods or in stem cell biology. In a first aspect, the invention provides a genetically-modified fish whose genome is homozygous for engineered or induced genetic alteration, e.g., an alteration that changes the sequence of the genomic ONA resulting in insertion and deletion of nucleotides that disrupt protein function or shift the frame of translation leading to premature protein termination, in one or more immune-related genes selected from the group consisting of: foxn1, rag2, jak3, prkdc, and interleukin 2-receptor gamma a and (IL2RGa and IL2RGb), wherein the genetic alteration results in an inactivation (i.e., loss of expression or function) of both alleles of the immune-related gene.