CYTOGENETIC ANALYSIS OF MALFORMED MOUSE FETUSES DERIVED FROM BALANCEDTRANSLOCATION HETEROZYGOTES

Reciprocal translocations are readily induced by various physical and chemical mutagens in certain germ-cell stages. Carriers of balanced re ciprocal translocations generally exhibit no abnormal phenotypes, exce pt for occasional male sterility, but about half (on average) of their progeny carry grossly unbalanced chromosome complements and die prena tally, so that the carriers are said to be 'semisterile'. Since death of such progeny generally occurs in very early embryonic stages, it wo uld be of minor importance in an analogous human situation. Several ty pes of unbalanced segregants, however, survive to late gestational or even to postnatal stages and are often malformed. Recently, it was det ermined in this laboratory that over one half of the male carriers of methylene-bisacrylamide-induced translocations, sired litters that had late-dying and/or malformed fetuses (Rutledge et al., 1990). Five hig h-anomaly translocation stocks derived from that study and four derive d from studies with other mutagens were analyzed cytogenetically to de termine (I) the chromosomes and breakpoints involved, (2) the nature o f chromosome imbalance in malformed fetuses, and (3) the types of meio tic segregation that produce late-surviving unbalanced segregants. Cyt ogenetic analysis of the 9 translocation stocks revealed 18 breakpoint s located in 12 chromosomes. Each translocation had at least one break point located near the centromere or the telomere. Ah translocations p roduced abnormal fetuses that were partially monosomic for a very shor t terminal chromosome segment, and partially trisomic for a segment th at can be of various lengths, 2-10 times as long as the monosomic segm ent. In 6 stocks, these abnormal fetuses arose by adjacent-1 or altern ate segregation; in the other three they arose by adjacent-2 segregati on. In addition, tertiary trisomy by 3-1 missegregation was also obser ved in two of the stocks.