Somatic Cell Genetics, Vol. 5, No. 5, 1979, pp. 585-595 Erythromycin Resistance in Mouse L Cells Peter L. Moiloy I and Jerome M. Eisenstadt Department of Human Genetics, Yale University School of Medicine, New Haven, Connecticut Received 21 February 1979-Final 30 April 1979 Abstract--The sensitivity of mouse cell lines in culture to the macrolide antibiotic, erythromycin stearate, was investigated. Both resistant and sensi- tive lines were found. Experiments indicated that in sensitive cells erythro- mycin stearate inhibits mitochondrial protein synthesis. Mutants resistant to erythromycin stearate were selected from the line LM(TK-), and these are also less sensitive to other macrolide antibiotics such as carbomycin and spiramycin. Attempts to transfer the erythromycin resistance of either the mutants or naturally resistant lines by fusion of cytoplasts with sensitive cells were unsuccessful, and it is concluded that resistance to erythromycin stearate is controlled by nuclear genetic factors. INTRODUCTION The assembly of functional mitochondrial respiratory oxidative phospho- rylation and protein synthetic systems requires the synthesis of gene products coded within both the nuclear and mitochondrial genomes. In lower euka- ryotes the use of mutants in all of these systems has contributed greatly to understanding their synthesis and assembly and has enabled the mapping of the genes for several products and investigation of the characteristics of the mitochondrial genetic system (1-3). Mammalian cell mutants resistant to chloramphenicol and carbomycin, inhibitors of mitochondrial protein synthesis, have been isolated (4-6). Resistance to chloramphenicol is cytoplasmically transferred (for review of system see ref. 7), while resistance to carbomycin is not transferred by enucleated cytoplasts. Recently the isolation of mutants resistant to the inhibitor of oxidative phosphorylation, rutamycin, has been reported (8). Other mutants with defects in enzymes of the respiratory chain have been 1Present address: Department of Biochemistry, University of Adelaide, South Australia. 585 0098-0366/79/0900-0585503.00/0 9 1979Plenum Publishing Corporation