USE OF HUMAN PLACENTAL ALKALINE-PHOSPHATASE TRANSGENES TO DETECT SOMATIC MUTATION IN MICE IN-SITU

Methods for in situ detection of cells that have suffered a specific m utation would be valuable for understanding somatic genetic mosaicism, a phenomenon that underlies a variety of diseases including cancer. S uch methods would also be valuable in studying changes in gene express ion, whether programmed by the cells or caused by exogenous forces, su ch as exposure to genotoxins or infection by a virus. To improve metho ds for detection of genetic change at the cellular level in animal tis sues, we used the human placental alkaline phosphatase (PLAP) gene. Th e FLAP gene sequence was modified such that it could no longer produce functional FLAP enzyme. Mutant FLAP genes were placed in the mouse ge nome, and populations of cells carrying these mutant FLAP genes were s tudied to determine the fraction of cells that would acquire FLAP acti vity. Spontaneous and induced reversion of mutant FLAP genes was studi ed in cultured cells and in the tissues of transgenic mice. The data o btained from these studies show the utility of in situ reporter genes such as FLAP for detection of variant cells within a tissue. (C) 1998 Academic Press.