Rita J. S. Phillips

'lurcher', A new gene in linkage group xi of the house mouse.

6. SummaryLurcher, Lc, a new mutant of the house mouse with neuromuscular action, is semidominant and is lethal in the homozygote, which dies soon after birth. The cause of death is not known. It is in Linkage Group XI, lying about 8 centimorgans beyondwaved-1 with respect toWhite. Lurcher females have smaller litters.

Gene-tagged chromosome translocations in eleven stocks of mice

SummaryThe cytogenetic problems of correlating linkage groups in the house mouse with their chromosomes, and of establishing the chromosomal independence of known linkage groups, call for the use of numerous genetically tagged translocations. Eleven new translocations have been induced and tagged; they involve linkage groups I, II, III, V, VIII, IX and XI.

MUTAGENIC EFFECTS OF REPEATED SMALL RADIATION DOSES TO MOUSE SPERMATOGONIA I. SPECIFIC-LOCUS MUTATION RATES

Abstract When male mice were given repeated small daily doses of 10 rad γ-rays at high dose rate (17 rad/min) the yield of specific-locus mutations was less than when the same total dose (600 rad) was given in a single exposure, and about the same as that after irradiation at low dose rate (0.008 rad/min). However, when a similar total dose was split into doses of 50 rad at weekly intervals the results depended on dose rate. The mutation rate after 12 × 50 rad X-rays at 66–70 rad/min was not significantly different from that after a single exposure, whereas the mutation rate after 12 × 50 rad γ-rays at 0.06 rad/min was typical of low dose-rate irradiation. This confirms that the effect of dose rate on mutation rate does not depend on continuity or close spacing of the exposures. However, it is suggested that the “small dose” effect depends both on size of each dose and on close spacing of doses.

A comparison of the mutagenic effectiveness of chronic neutron- and γ-irradiation of mouse spermatogonia

Abstract Hybrid male mice were given a dose of 214 rad fast fission neutrons (plus 93 rad γ-contamination) over twelve weeks, while brothers were given 606 rad γ-radiation (plus 2.5 rad neutron contamination) over the same period. Six weeks later they were mated to females homozygous for recessive alleles at seven specific loci. Neutron-irradiated mice remained sterile for a further four weeks but γ-irradiated mice showed no sterile period. Testis weight fell to less than 20% during neutron irradiation, but to about half normal during the γ-irradiation. The frequency of specific locus mutations was 22.9 · 10 −5 /locus in the neutron series and 3.9 · 10 −5 /locus in the γ-series, from which induced mutation rates of 100.6 · 10 −8 /rad for neutrons and 4.4 · 10 −8 /rad for γ-rays were derived, after allowing for spontaneous mutations. Thus the RBE for neutrons is about 23 in these circumstances. A figure of about 20 was arrived at by analysing data on dominant visible mutations. There were indications that chronic neutron exposures were also much more effective than chronic γ for the induction of reciprocal translocations and other chromosomal changes. However, the sex ratio was very similar in the two series. Most of the dominant and recessive mutations tested proved to be homozygous lethals; there were also signs that carriers of newly arisen specific locus mutations were more likely to die before weaning age than non-carriers. So the true specific locus mutation frequencies are probably higher than those given here.

Dose-response curves for radiation-induced gene mutations in mouse oocytes and their interpretation.

Previous work, in which female mice had been given fractionated doses of 20 X 10 rad X-rays, had confirmed and extended Russells observations that the dose-response relationship for specific-locus mutations in mature-mouse oocytes is curved at low doses. The present work was intended to study the relationship at relatively high doses. Adult female mice were given doses of 200, 400 or 600 rad x-rays at 52 or 72 rad/min, and mated immediately. Offspring conceived in the first 7 days (i.e. using oocytes which were mature at time of treatment) were scored for specific-locus mutations. The data indicate that the departure from linearity of the dose-response curve is marginally significant at the 5% level. A quadratic dose-response curve (y = c + aD + bD2) and a square-law relationship (y = c + bD2) both give a good fit to the data. Both curves fit data of other authors obtained at low doses or dose-rates. These results could be interpreted either in terms of dose-dependent repair phenomena, or by considering specific-locus mutations as two-track events. In view of knowledge of other phenomena concerning mutation and cell killing in mouse oocytes, such as the variation in sensitivity of different cell stages, the interpretation in terms of repair phenomena is preferred.

Crossing-over in mice heterozygous for t -alleles

FOR studies of mutagenesis in the house mouse it would be very useful if there were chromosome changes acting as crossover suppressors, which could be used to build up stocks resembling in function the C1B and Muller-5 stocks of Drosophila melanogaster. The only crossover suppressors so far known are some of the recessive lethal t-alleles in linkage group IX. The experiments reported in this paper were

THE GENETIC SENSITIVITY TO X-RAYS OF MOUSE FOETAL GONADS

The mutation rate at seven specific loci was measured among the offspning of male and female mice exposed as 17-day-old fetuses to 200-r x rays. In the female series, the mutation rate was lower, by a factor of about 4, than in the comparable adult rats; in the mae series, the mutation rate was lower but not stastiatically significantly lower tuan in adults. (auth)

The ineffectiveness of chronic irradiation with neutrons and gamma rays in inducing mutations in female mice

Abstract Hybrid female mice were exposed to 412 rads 60Co γ rays or 80 rads fast neutrons (+ γ contamination) in 12 weeks and the amount of genetic damage in offspring was compared with controls. Frequencies of specific locus recessive and of dominant visible mutations were very low in the irradiated series, differing little from the control frequencies of nil. There were no significant differences between the sex-ratios of offspring in the three series, thus no evidence for the induction of sex-linked lethal mutations. No estimates can be given of the relative genetic effectiveness of chronic neutron and γ exposures in female mice, but the specific locus mutation frequency after the neutron dose was less than 5 per cent of that obtained in male mice after spermatogonial irradiation with a similar dose over the same 12-week period. It is now clear that both acute and chronic exposures of the immature mouse oocyte to both high and low LET radiations result in minimal genetic damage. It is still not clear w...

A test for mutagenicity of caffeine in mice

Summary1.The results are given of an experiment comparing the specific locus mutation-rates in male and in female mice having 0.1% caffeine dissolved in their drinking-water up to the age of ten weeks. Their parents had the same treatment from the time of mating, so that the tested germ-cells might be exposed to caffeine during embryonic development.2.The mutation-rates in males and females did not differ significantly from each other, nor from the known spontaneous rate; thus there was no evidence for induction of mutations by the caffeine treatment. Neither was there evidence for the induction of dominant lethals following caffeine treatment of males.3.The treatment did not noticeably affect reproduction, but some mice developed aggressive tendencies towards their cage-mates. Some mice were kept on 0.1% caffeine throughout life: they continued to breed satisfactorily on the whole.

Specific locus mutation rates after repeated small radiation doses to mouse oocytes

When female mice were given a dose of 20 X 20 rad X-rays, the specific locus mutation rate among offspring conceived up to 7 weeks after the end of treatment was 1/39887 or 0.18-10(-7)/rad/locus, whereas when the same total dose of 200 rad was given in a single exposure the mutation rate was 9/34813 or 1.85-10(-7)/rad/locus. The lower mutation rate after the 20 X 10 rad dose was obtained whether the total or 200 rad was given over a period of 5 days or 4 weeks, and if only young conceived in the first 20 days, rather than 7 weeks, were considered. It is suggested that each 10 rad fraction had the same small effect, and hence that these results confirm and extend RUSSELLs previous finding that the dose-response relationship for specific locus muations in females is curved.