THE INHERITANCE OF SUSCEPTIBILITY TO THE TERATOGENIC ACTION OF CORTISONE IN MICE
T has been found (FRASER and FAINSTAT 1951) that pregnant mice given I cortisone during gestation will give birth to offspring a certain proportion of which have cleft palates. The frequency with which this deformity appears was observed to depend on : 1) the genotype of the treated animal, strain A being " susceptible," C57BL relatively " resistant," to this effect of cortisone; 2) the dose of the hormone administered, too small an amount being ineffective in producing cleft palates, too great
... palates, too great an amount causing resorption of the entire litter; and 3) the time during the gestation period when the animal was treated. The investigation reported here has provided fiirther observations on the genetics of susceptibility to the teratogenic effects of cortisone. MATERIALS A N D METHODS The animals used in this study were the A/Jax and C57BL/6Jax inbred strains of mice, F1 females of reciprocal crosses between these strains, and females of the first backcross to strain A. Three or four females and one or two males were kept in each breeding cage. They were fed water and Purina Fox Chow ad libitunc, supplemented twice a week by lettuce and white bread soaked in. milk. The breeding cages were examined periodically for females which were palpably pregnant and for females with vaginal plugs. All females which were palpably pregnant or had vaginal plugs were placed in separate cages where they were treated and remained for the duration of their pregnancies. After delivery the females were returned to their original breeding cages. The offspring were examined for gross abnormalities and then discarded or fixed in Bouin's solution for future histological study. Pregnant females were given 2.5 mg of cortisone acetate (ll-dehydro-17hydroxycorticosterone-21-acetate, Merck) for four successive days (called 4 x 2 5 mg cortisone) intramuscularly in the flank. It had previously been established that this dose of the hormone caused a relatively high incidence of cleft palate with a relatively low frequency of resorption of litters. The fluid in which the hormone is suspended has no gross effect on development ( FRASER and FAINSTAT 195 1 ) . 1This paper is taken from a thesis submitted to the Faculty of Graduate Studies and Research, McGill University, in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Length o/ gestation in days measured from observation of vaginal plugs tp p a r turition for females o f strains A , C57BL (= B), and the F, and backcross (BC) generations. Length of gestation in days 15 16 17 18 19 20 21 22 23 Cross Total Mean f S.E.