GENE TARGETING IN NORMAL SOMATIC-CELLS - INACTIVATION OF THE INTERFERON-GAMMA RECEPTOR IN MYOBLASTS

Gene targeting in somatic cells represents a potentially powerful meth od for gene therapy, yet with the exception of pluripotent mouse embry onic stem (ES) cells, homologous recombination has not been reported f or a well characterized, non-transformed mammalian cell. Applying a hi ghly efficient strategy for targeting an integral membrane protein - t he interferon gamma receptor - in ES cells, we have used homologous re combination to target a non-transformed somatic cell, the mouse myobla st, and to compare targeting efficiencies in these two cell types. Gen e-targeted myoblasts display the properties of normal cells including normal morphology, ability to differentiate in vitro, stable diploid k aryotype, inability to form colonies in soft agar and lack of tumorige nicity in nude mice.