The experiment was designed to form a bridge between the results of specific-locus experiments, using only a few gene loci, and those using the whole genome of the mouse. Male mice were given 600 r acute X-rays and bred from in such a way that at successive stages mutation in spermatogonia to dominant visibles and lethals, dominant semisteriles, recessive visibles and recessive lethals could be measured. The data concerning dominant mutations were relatively few but confirmed previous results. No recessive visible mutations were found, and the upper fiducial limit to the induced mutation rate to recessive visibles was set at a value 4500 times the rate to viable specific-locus mutations. From the attempt to measure recessive lethal mutations two interesting points emerged. The first was that granddaughters of the irradiated males had fewer corpora lutea per pregnancy than granddaughters of the control males, and the second was that this difference in number of ova shed was not reflected in any difference in litter-size at birth. Since this suggests intra-uterine compensation, no attempt was made to calculate mutation rates to recessive lethal genes from these data. The implications of the results are discussed.

The mutant doublefoot, Dbf, of the mouse arose spontaneously, and was shown to be inherited as an autosomal dominant, mapping 9–13 cM proximal to leaden, ln, on chromosome 1 and showing no recombination with the microsatellite markers D1Mit24 and D1Mit77. In heterozygotes the phenotype includes many extra toes on all four feet, and the tibia and fibula may be reduced and bowed. The head is shortened and broad and the eyes are held half-closed, and some animals develop hydrocephalus. The tail is kinked and abnormally thick, and the soles of the feet are swollen. Growth is retarded, viability is reduced, and reproduction is impaired in both sexes. Only about 30 % of males are normally fertile, and testis weights and sperm counts may be reduced, although this appears not to be the main cause of poor fertility. In females vaginal opening is delayed and oestrous cycles are irregular, although the animals appear to respond to gonadotrophic hormones. Crosses of Dbf/ + × Dbf/ + are very poorly fertile. Prenatally, Dbf/ + heterozygotes can first be recognized at 11½ days gestation by abnormally broad fore limb buds. Putative Dbf/Dbf homozygotes at 12½ days have similar limbs defects and also split face, due to failure of the maxillae to fuse in the midline. Some homozygotes and a few putative heterozygotes have cranioschisis. At 13½ days, the heads of homozygotes tend to bulge in the frontal region and a bleb of clear fluid is visible medially. At 14½ days Dbf/Dbf fetuses may have oedema and some are dead. From 15½ days onwards no live Dbf/Dbf fetuses have been found. The gene maps close to the locus of Pax3, but crossovers between Dbf and Pax3 have been found, ruling out the possibility that a gain-of-function mutation in Pax3 might be involved.

A mutation to an apparently new allele at the W-locus of the mouse arose spontaneously in a cross between two inbred strains. Heterozygotes have a broad white sash, leading to the name and symbol sash, Wsh. Homozygotes are black-eyed whites which are viable, fertile and not anaemic, although the gene does cause mild haematopoietic defects. The original mutant animal also carried a spontaneous recessive lethal mutation on chromosome 5, mapping at 2 cM distal to the W-locus.

Previous measurements of specific locus mutation rates in mice had all involved the seven loci, a, b, c, d, p, s and se. An experiment was performed with the same mouse stock (C3H × 101) and the same radiation dose (600 rad) to spermatogonia as had been used previously, but employing a new group of six loci, a, bp, fz, In, pa and pe. The observed mutation rate, 5·0 × 10−8 per locus per rad, was significantly lower than that for the original seven loci, but was three to four times higher than the corresponding mutation rate in Drosophila melanogaster.

The frequency of adjacent-2 disjunction in mice carrying the reciprocal translocation T(9; 17)138Ca was studied by mating together animals heterozygous for the translocation and carrying different recessive marker genes, using Tt for chromosome 17 and cwcw for chromosome 9. The proportion of marked young arising from adjacent-2 disjunction varied according to the markers carried in the two parents. When the female carried Tt the frequencies of marked young were always higher than when non-T females were used, and when Tt and cwcw were carried in the same parent there was a shortage of marked young obtaining both copies of the proximal region of chromosome 17 from the father. Both these effects were regarded as probably another example of the phenomenon discovered by Johnson, of inviability of young lacking a maternal homologue of a certain region of chromosome 17. There were other variations in frequency of marked young, among crosses using non-T females, which may have been due to differences in transmission ratio of male gametes carrying various t-haplotypes or to true variations in frequency of adjacent-2 disjunction.

An allele of the mouse brachyury locus, T22H, had been shown previously to involve a deletion of several markers in the proximal part of chromosome 17, and almost certainly includes deletion of the t-complex distorter gene Tcd-1. The effects of T22H on transmission ratio distortion and male sterility caused by the t-complex were compared with those of a partial t-haplotype th51, which carries the t-form of the distorter Tcd-1t. In combination with the complete haplotypetf32, T22H caused severe impairment of male fertility, but males of genotype T22H/t6 or T22H/thSl were normally fertile. These results were very similar to those obtained when th51 was in combination with the same haplotypes. In effect on transmission ratio T22H was again similar to thSI, in that it produced a marked increase in the transmission of the haplotype t6. To test whether the effects of T22H were due to deletion of elements other than Tcd-1, the effect of T22H on transmission of the partial haplotype th2 was compared with that of the deletion Thv. Again T22H markedly increased transmission of the t-haplotype and the effect was significantly greater than the small effect produced by Thp.

It is concluded that deletion of the distorter Tcd-1 has an effect like that of the t-form of this distorter, Tcd-1t, and hence that Ted-11 must be an amorph or hypomorph. It is speculated that other t-complex distorters, Tcd-2t and Tcd-3t may also be amorphs or hypomorphs. Thus, the phenomena of transmission ratio distortion and male sterility due to the t-complex appear to be brought about by differential susceptibility of wild-type and t-responder alleles, Tcr+ and Tcrt, to a shortage of distorter gene product.

The lethal t-haplotypes of the mouse fall into several distinct complementation groups, and varying degrees of partial complementation occur when haplotypes from different groups are crossed. The haplotype th20 arose as a mutant from the haplotype t6, and is thought to include a small deletion covering loci near the t-lethals. In this paper the complementarity of th20 was compared with that of its parent haplotype t6. th20 showed weaker complementation than t6 of the haplotypes tw5, tw32 and tw1. Hence the loci of these lethals were probably exposed by the deletion in th20. However, th20 showed full complementation of tw18 and showed full viability in compound with the dominant brachyury allele hairpin-tail, Thp. Therefore, the th20 deletion probably does not overlap the presumed deletion in Thp, nor extend to the locus of the tw18 lethal. The significance of the weak complementation of tw5, tw32 and tw1 is discussed.

The radiation-induced agouti allele a1 is recessive to the alleles a and a4H (which resembles ae). It is lethal when homozygous and also in combination with the dominant yellow allele Ay. The ethylnitrosourea induced allele a16H is also lethal when homozygous, and when heterozygous with a shows a phenotype like that of ax, with black back and lighter belly. Like ax it is not lethal with Ay, and it is also not lethal with a1, a1 is believed to be the first recessive allele which is lethal with Ay, and may be useful in elucidating the complexity of the agouti locus.

In order to test the feasibility of preservation, of genetic stocks of mice by storage in liquid nitrogen, mouse embryos at the 8-cell stage, were frozen and stored in liquid nitrogen at – 196 °C under increased radiation exposures of 1·8×, 9× and 84× background levels for periods of 6–8 months, 10–12 and 27–29 months, the 1·8 × level being regarded as a control. Their survival rates to the blastocyst stage, and after transfer to recipient females, to foetal or liveborn stages were then compared with those of unfrozen or short term frozen control embryos. The freezing process per se caused a marked loss of viability, in comparison with the unfrozen controls, but at the 1·8× radiation level there was then no further loss in viability even at the longest storage time (27–29 months). Similarly, at the 9× radiation level there was no loss of viability during storage up to 29 months, but at the 84× level the proportions of implanted embryos and live foetuses were slightly reduced. It was not clear if this was a true effect of radiation, since it was not related to time of storage. Considering all groups, about 20–30% of the embryos originally frozen were recovered as foetuses or liveborn young. It is concluded that the preservation of genetic stocks by storage in liquid nitrogen is a feasible proposition.

The fact that the X-linked genes scurfy (sf) and sparse-fur (spf) of the mouse do not produce a mosaic effect in heterozygotes had been taken, by other workers, together with results from X-Autosome translocations, as evidence that inactivation of the mouse X was incomplete. In this paper it is argued that absence of a mosaic effect is not adequate evidence that a gene is not inactivated. The argument was backed by an experiment in which the spf gene was introduced heterozygously into females carrying an X-linked translocation resulting in non-random X-inactivation with the same X active in all cells. When the mutant (spf) allele was on the active X its effect was fully expressed, indicating that the normal allele on the structurally normal inactive X was undergoing inactivation. Argument is further presented that results from X-Autosome translocations do not indicate the degree of completeness of inactivation in a structurally normal X. Hence, there is no evidence that inactivation of the mouse X is incomplete, although evidence from XO females does suggest that it may be incomplete in man.

The t-complex on mouse chromosome 17 results in transmission ratio distortion in males heterozygous for complete haplotypes, and sterility in those homozygous for semi-lethal or doubly heterozygous for complementing lethal haplotypes. This sterility is due to inability of spermatozoa to fertilize. The haplotype th7 is an unusual laboratory-derived haplotype, postulated to carry a small duplication of t chromatin. Males heterozygous for th7 show a new form of sterility, apparently due to failure to form copulation plugs during mating. This is accompanied by a strong propensity to acute urinary obstruction. It is suggested that both the failure to form copulation plugs and the urinary obstruction are due to some abnormality in function of the accessory sex glands, and are the result of incorrect dosage of a gene in the postulated duplication. The symbol Msu for male sterility and urinary obstruction is suggested for the locus concerned. Previously a recessive form of abnormal behaviour had also been attributed to this duplication.

Mouse mutant genes which result in defects similar to those of medical importance in man may be of value as models for the study of the defect concerned. We report here a new gene causing congenital cataract in the mouse, which may be useful in the understanding of cataract in man.

A further point of interest is that Kratochvilova & Ehling (1979) have recently developed a new method of measuring increased mutation rates in the mouse, by examining offspring of animals treated with mutagens for the presence of cataracts due to mutant genes. For the purposes of this test it is valuable to have information on the number and map position of loci which can mutate to give cataracts.

The locus of the gene striated, Str, on the mouse X-chromosome, was previously reported to be on the side of tabby (Ta) away from bent-tail (Bn). Results given in the present paper show this report to have been incorrect, and that the order of loci is Bn-Str-Ta-(Mo-Blo). In addition, the position of the translocation break in Searle's translocation (T1GH) has been confirmed, the order of loci with respect to T16H being Bn-T16H break-Ta-Blo.