A test for neutrality of mutations of the lacZ transgene.

Neutral mutations are stable alterations in DNA that are neither beneficial nor damaging to the cell. Once a mutation is fixed in the DNA, the mutant frequency should increase to its maximum and plateau thereafter, provided that enough expression time is given. Evidence has been obtained indicating neutrality for the endogenous Dlb-1 locus and for the lacl in the BigBlue transgenic system, and is reported here for lacZ in the Muta Mouse system. We have found that, after an acute dose of ethylnitrosourea (ENU, 250 mg/kg) the mutant frequency for both lacZ transgene and Dlb-1 remained constant between 10 and 70 days after mutagenesis in the small intestine, where cell turnover is rapid (approximately 7 days). The same concept should apply to other tissues.