R. G. Edwards

Genetic radiosensitivity of specific post-dictyate stages in mouse oöcytes

The induction of dominant lethals after X-irradiation of dictyate, later meiotic stages, and the pronuclear stage after fertilization have been compared using the technique of induced ovulation in mice. The injection of gonadotrophins ensures that the time at which the synchronously dividing oocytes reach any particular meiotic stage is accurately known. Embryonic lethality up to 13½ days was studied after 0 r., 100 r. and 200 r. acute X-irradiation. Metaphase I, anaphase I and metaphase II were the most sensitive stages, with LD 50 s of about 120 r., 130 r. and 170 r. respectively. The dictyate and pronuclear stages were much less sensitive, with LD 50 s in the region of 500 r., and sensitivity rose steeply during prophase I. Numbers of corpora lutea decreased with irradiation, the decrease being greatest with irradiation at metaphase I and anaphase I. The ovulation of large numbers of eggs, which increased the preimplantation loss of embryos above normal, and the low luteal counts probably masked lethality to some extent. Results generally agree well with those reported in a number of plant and animal species.

The size and endocrine activity of the pituitary in mice selected for large or small body-size

The large alterations in body-weight arising after several generations of selection for large or small body-size clearly involve basic physiological processes. In previous papers we have described various physiological differences between mice of large and small body-size, using two strains (N and C) selected by Falconer (1953, 1960). Mice of the large line of strain N (NL) grow considerably faster and contain a higher proportion of body fat than mice of the small line (NS) (Fowler, 1958). NL mice consume more food and absorb a greater proportion of nitrogen from it, but differences in food utilization appear to be largely a consequence of the different growth rates of the two lines (Fowler, 1962). Physiological changes of a more fundamental nature are clearly involved in determining adult body-weight, and the basic endocrine pattern of large and small mice is an obvious choice for study. Earlier work on the reproductive physiology of strains N and C indicated that differences existed between mice of the large and small lines of both strains in the amounts of pituitary gonadotrophins secreted (Fowler & Edwards, 1960). Sterility in line NS, which appeared to be due to a general deficiency in the secretion of the gonadotrophic and pregnancy hormones, became acute during the present experiment, and severely limited the number of NS mice available for study. NL mice have a higher energy expendtiure than NS mice, though the expenditure is similar in the two lines and in the control line (NC) when animals of the same weight are compared (Fowler, 1962). In the present experiments, adult mice of strain N were used in studies of pituitary weights, gonadotrophic activity of the anterior pituitary, thyroid activity, and alterations in growth rates following the injection of growth hormone. Mice related to line CL were also available and were included in some of the studies.

‘ Midget ’, a new dwarfing gene in the house mouse dependant on a genetic background of small body size for its expression

Midget , a new dwarfing gene in the house mouse, was found in a line ( NS ) selected for small body size. Backcrosses to, and heterozygous matings of NS mice gave midget offspring in the expected 1:1 and 1:3 ratios. Backcrosses to two other lines of mice selected for small body size resulted in fewer midget offspring than expected and in a reduced phenotypic expression of the gene, though matings between these midget offspring gave all midget progeny. A characteristic check in growth occurred between 15 and 21–24 days of age, and midgets rarely exceeded 10 g. at 6 weeks of age. They were 1·2 g. lighter than NS litter-mates at 3 weeks, and 3·6–4·4 g. lighter at 6 weeks. Fostering or transferring 3½-day-old midget embryos to the uteri of large mothers slightly increased the growth-rate, though the characteristic growth check still persisted. Transfer as embryos did not influence the midget phenotype. Midget males were of near-normal fertility. The females were semi-sterile due to irregularity or absence of oestrous cycles, failure to ovulate, or the death of embryos before implantation. Each of these factors, which were also found in NS mice, could be remedied by the administration of exogenous hormones. The genetic factors underlying the expression of midget are discussed, and the physiological traits associated with this and with other dwarfing genes are compared.