Developmental Anomalies in Mice Resulting From Action of the Gene, Disorganization, a Semi-Dominant Lethal

DISORGANIZATION, symbol Ds, arose as a spontaneous mutation in a newly inbred strain of mice and has been maintained and studied in a heterogeneous population. It received its name from the fact that it disrupts the orderly processes of organogenesis and induces a great variety of developmental anomalies in structures derived from all germ layers. Studies in inheritance have shown Disorganization to be a Mendelian unit, semidominant, usually lethal in homozygotes and with incomplete penetrance (72%) in heterozygotes. Little is known of the homozygote; preliminary studies have indicated that it dies in the uterus after implantation, and ratios of abnormal to normal phenotypes from matings between heterozygotes indicate that few, if any, of the homozygotes survive to term. The heterozygote, on the other hand, survives to term and dies after birth only if the nature of the abnormality precludes postnatal survival. Heterozygotes are either abnormal in a great variety of ways or are normal overlaps. Penetrance, the incidence of affected individuals, is slightly greater in females than males, but does not vary with the phenotype (abnormal or normal) and sex of the parent having the Ds+ genotype. Moreover, neither maternal age nor parity appears to affect penetrance. However, when heterozygous animals were mated with mice of inbred strains, there were differences in penetrance ranging from 9% in 129 hybrids to 89% in C3H hybrids. The genetic environment in which Ds acts was thus found to influence penetrance. There were also indications from reciprocal crosses with mice of strains 129 and C3H that uterine environment may also influence penetrance. In the C3H ♀ X Ds+ ♂ cross, penetrance was 89% and, in the reciprocal cross, 57%, indicating an enhancing intrauterine influence in the C3H mice. Penetrance was 9% in the 129♀ X Ds+ ♂cross and 37% in the reciprocal, indicating a suppressing intrauterine influence in mice of strain 129. In matings to mice of the heterogeneous stock and of strain DBA/1, there were no differences in the reciprocal crosses. These observations may have little validity since the male and female carriers of Ds were of heterogeneous stock with the possession of only one allele in common, but they seem worth comment to those interested in the interaction of heredity and environment. The expression (types of anomalies) and expressivity (degree of defect), unlike penetrance, did not vary with parental genotype.