ON THE FATE OF ORALLY INGESTED FOREIGN DNA IN MICE - CHROMOSOMAL ASSOCIATION AND PLACENTAL TRANSMISSION TO THE FETUS

We have previously shown that, when administered orally to mice, bacte riophage M13 DNA, as a paradigm foreign DNA without homology to the mo use genome, can persist in fragmented form in the gastrointestinal tra ct, penetrate the intestinal wall, and reach the nuclei of leukocytes, spleen and liver cells. Similar results were obtained when a plasmid containing the gene for the green fluorescent protein (pEGFP-C1) was f ed to mice. In spleen, the foreign DNA was detected in covalent linkag e to DNA with a high degree of homology to mouse genes, perhaps pseudo genes, or to authentic E. coli DNA. We have now extended these studies to the offspring of mice that were fed regularly during pregnancy wit h a daily dose of 50 mu g of M13 or pEGFP-C1 DNA. Using the polymerase chain reaction (PCR) or the fluorescent in situ hybridization (FISH) method, foreign DNA, orally ingested by pregnant mice, can be discover ed in various organs of fetuses and of newborn animals. The M13 DNA fr agments have a length of about 830 bp. In various organs of the mouse fetus, clusters of cells contain foreign DNA as revealed by FISH. The foreign DNA is invariably located in the nuclei. We have never found a ll cells of the fetus to be transgenic for the foreign DNA. This distr ibution pattern argues for a transplacental pathway rather than for ge rmline transmission which might be expected only after long-time feedi ng regimens. In rare cells of three different fetuses, whose mothers h ave been fed with M13 DNA during gestation, the foreign DNA was detect ed by FISH in association with both chromatids. Is maternally ingested foreign DNA a potential mutagen for the developing fetus?