Transgenic animals are being used as models of human generic disorders and for investigation of the effects of targeted correction or gene disruption in whole animals. Chromosomal integration and stable germ line transmission of novel transgenes allow study of the expression of these genes at any point in the development of the transgenic organism, as well as at any point in the pedigree of the transgenic line. The potential use of transgenic fish as model systems for higher vertebrate disease research has not been extensively developed. A well suited animal for development of a valuable nonmammalian transgenic system in fish is Oryzias latipes or medaka. Medaka provide investigators with abundant daily egg production, inexpensive maintenance, and very well documented embryological development. The Xiphophorus fish genetic system has already provided valuable insight into the genetic determinants of oncogenesis. The Xiphophorus gene map is the most extensive available in nonmammalian vertebrates. Current research efforts involve isolation of Xiphophorus genes homologous to human genes involved in DNA repair and oncogenesis. Microinjection of medaka eggs with Xiphophorus DNA repair genes, oncogenes, and tumor suppressor genes followed by establishment of homozygous transgenic stocks would provide a vertebrate system amenable to elucidation of the effects which expression of transgenes may have on development, or vice versa. Isolation and DNA sequence determination of medaka genes will allow attempts at gene disruption via targeted recombination. Medaka stocks to be constructed may contain several transgenes, allowing assessment of gene interaction in the transformative process. This system, if developed, will further our understanding of the multiple genetic events which are thought to occur in tumor development.
