Systematic approach to the study of trisomy in the mouse. II.

In pursuit of attempts at a systematic study of autosomal trisomy in the mouse, an experimental model is presented which permits the induction of specific trisomic conditions. It is based on (1) the occurrence of considerable rates of meiotic anaphase I malsegregation of double metacentric heterozygotes with monobrachial homology, (2) the expectation that trisomics may be found among the unbalanced conditions in the progeny of crosses of the double heterozygotes with "all acrocentric" mice, and (3) the observation that trisomy, in contrast to monosomy or combined monosomy plus trisomy, is the only unbalanced condition surviving beyond day 10. In this design, the specific nature of the trisomy is predetermined by the choice of the double metacentric heterozygote combination and recognized by such criteria as chromosome arm number and the presence of both metacentrics. All trisomic conditions of the mouse so far studied inevitably lead to early or late fetal death. Although the possibility of a systematic survey of all 19 possible autosomal trisomies in the mouse can be anticipated, this report is limited to a study of trisomies (Ts) 1, 8, 11, 12, and 17. Ts 8, 11, and 17 cause severe developmental inhibition at an early stage of development. Death occurs about day 11 or 12. Ts 1 displays a syndrome of moderate to marked developmental retardation and slight to more distinctly disproportionate hypoplasia. These embryos may survive until day 15. In contrast, a lesser extent of hypoplasia and retardation is observed in Ts 12, which, however, almost regularly shows exencephaly and microphtalmia. Obviously, variation of the severity of phenotypic manifestation of the trisomic conditions is due to genic heterogeneity of the animals used in the present study. Current attempts are directed to introduce a sufficient number of metacentrics in a defined background, thus providing the means for future systematic studies of the phenotypic expression of gross genomic imbalance.