Tests of induction in mice by acute and chronic ionizing radiation and ethylnitrosourea of dominant mutations that cause the more common skeletal anomalies.

Assessment-of-Dominant-Damage (ADD) experiments explored induction by proven specific-locus mutagens of dominant mutations that cause skeletal anomalies, cataracts, and stunted growth in offspring of mutagenized male mice. The data set reported here includes 6134 offspring. Mutagenic treatments included 600 R (i.e., approximately 6 Gy) of X-rays delivered in about 7 min, 600 R of gamma rays delivered over about 110 days, and four weekly intraperitoneal (i.p.) injections of 77.5 mg/kg of ethylnitrosourea (ENU). The results reported in this paper are restricted to mutations induced in stem-cell spermatogonia and to the 34 more common skeletal anomalies (i.e., those found in 0.5% or more of the control offspring). Mutation induction was demonstrated for eight anomalies in the acute X-ray experiment and for 17 anomalies (including those same eight anomalies) in the ENU experiment. In spite of the surprisingly high mutation rates found for these treatments, there was no hint of any induction of such dominant mutations by 600 R of chronic gamma radiation. Our results suggest that several anomalies related to variation in the sacralization pattern may be particularly useful for revealing induction of dominant mutations.

Description of first germinal mosaic mutation identified in dominant skeletal mutation experiments and considerations about how to deal with this kind of spontaneous mutation in analyses.

Germinal mosaicism is a well-established mechanism by which new spontaneous mutations enter the human population, but it is only rather recently that clusters of mutations arising in that way have been acknowledged and dealt with in specific-locus experiments on male mice. This paper reports the first cluster of germinal mosaic mutations to have been identified in experiments on the induction of dominant skeletal mutations. The mutation was detected in six offspring of a control male from the radiation part of an Assessment-of-Dominant-Damage (ADD) experiment. Reasons are provided to explain why this one litter of six mutants was excluded from the analysis of induction of dominant mutations causing the more common skeletal anomalies, which is reported in another paper. The effects of excluding this litter from that analysis are fully described. There is discussion of why such clusters should be included in some analyses but omitted in others. They should certainly always be reported because, in some cases, they can have a major impact on conclusions. Details on this one cluster of FCGM mutations provide numerous examples of how a dominant skeletal mutation that causes rare effects can also cause many of the more common anomalies.