Influence of sex-linked genes on embryonic sensitivity to cortisone in three strains of mice.

It was postulated that sex-linked genes affecting embryonic sensitivity to cortisone-induced cleft palate and cortisone-induced resorption might differ between inbred mouse strains showing pronounced reciprocal effects. The three strains tested were the A/J (A), C57BL/6J (B), and C3H/HeJ (C), whose sensitivities to cortisone-induced cleft palate had been shown to be: A > C > B. The sensitivity of reciprocal A X B and B X C hybrid embryos was matroclinous; of reciprocal A X C embryos, patroclinous. Backcrosses of reciprocal FI hybrid males to inbred females were used to test the hypothesis of sex-linkage with respect to the incidence of cortisone-induced cleft palate, cortisone-induced resorption, and the overall level of cortisone-induced fetal damage. The results were consistent with the hypothesis that sex-linked genes affecting embryonic sensitivity to cortisone-induced cleft palate, but not to cortisone-induced resorption, differ in the three strains. The incidence of cortisone-induced cleft palate (CP) is greater in A/J than in C57BL/6 mice (Fraser and Fainstat, '51). The matroclinous sensitivity of offspring of reciprocal crosses between the A/J and C57BL/6 strains was shown to be independent of cytoplasmic factors (Kalter, '54). In analogous crosses between A/J and the relatively resistant C3H strain, Kalter ('65) found patroclinous sensitivity in reciprocal F, embryos. Patroclinous sensitivity was also found in offspring of reciprocal crosses between the A/St and C3H strains (Loevy, '62, '63). Between the C3H and C57BL/6 lines, however, matroclinous sensitivity obtains; C3H was found to be more sensitive than C57BL/6 (Francis, '71). On the basis of these studies a model was constructed for sex-linked inheritance of sensitivity to cortisone-induced CP, which accounts for the observed pattern of matroclinous and patroclinous sensitivities in the offspring of reciprocal crosses between the A/J, C57BL/6, and C3H/HeJ strains, hereafter referred to as strains A, B, and C, respectively. The model states that, whereas the relative sensitivities of the three lines to cortisone-induced CP are A > C > B, the contributions of X-linked genes to sensitivity are Xc > XA > X,. (Xc represents the TERATOLOGY, 7: 119-126, hypothetical X-linked gene found in the C strain, X, its allele in the A strain, and Xe the corresponding alleIe in the B strain. ) Since sensitivity to cortisone-induced CP is affected by maternal factors as well as by several genes (Fraser et al., '54; Kalter, '54; Loevy, '63), reciprocal backcrosses were used to test the hypothesis of sex-linkage. Male ' offspring of reciprocal crosses between inbred lines differ in the origin of their sex chromosomes. If such F, males are backcrossed to the parent strains, female offspring of the reciprocal backcrosses will differ in one X-chromosome. The cytoplasmic inheritance and prenatal environments do not differ between such crosses. In the present study parallel matings of hybrid females to inbred males were used as control matings. Offspring of such crosses differ in their cytoplasmic inheritance only. The inheritance of sex-linked genes for the six pairs of reciprocal backcrosses of the present study is shown in table 1. Received Mar. 17, '72. Accepted Nov. 10, '72. 1 Supported by NIH grant 5 TO1 GM00071. The contents of this paper form a part of the author's dissertation submitted as a partial requirement for the Ph.D. degree at the University of Michigan under the direction of Professor Morris Foster. 2 Present address: Research Associate, Department of Animal Science, Animal Genetics Laboratory, University of Illinois, Urbana, Illinois 61801.