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 genie 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.

In the backcross progeny of single (Robertsonian) metacentric heterozygotes of the mouse, segregational impairment of fertility and reduced litter size are initiated by misdivision of trivalents in meiotic anaphase I. Males heterozygous for the metacentrics Rbl, Rb4, Rb5, and Rb7Bnr of the tobacco mouse series and for the Rb8–10Bnr metacentrics derived from other feral domestic mice produce variable rates of meiotic malsegregation, ranging from 4 % to 26 % unbalanced M II figures. Chromosomally unbalanced gametes become involved in fertilization and produce aneusomic zygotes. Fetal aneuploidy causes developmental breakdown and prenatal death. Mono-somic zygotes are eliminated at an early stage of development. Most aneuploid embryos observed beyond day 8 or 10 of gestation were trisomics. Aneuploidy (trisomy) of the zygotes was considerably more frequent in the progeny of heterozygous females than in that of heterozygous males. There was evidence that this disparity might be the result of a higher nondisjunction rate in the female gametogenesis. Mechanisms of selection against unbalanced male germ cells might operate on a small scale. The highest incidences of aneuploid implants were found (with decreasing frequencies) in the backcross progeny of the Rb(1.3)l, Rb(16.17)7, and Rb(11.13)4Bnr female heterozygotes. With the experimental design used in this study, several trisomic conditions could be observed and their phenotype and developmental profiles described, namely, trisomies (Ts) 1, 3, 4, 10, 11, 12, 13, 16, and 17. Among these, Ts 3, 11, and 17 were characterized by severe developmental impairment and relatively early death, whereas the others could survive until day 13 to 15 or, as in the case of Ts 12, even until day 17. Ts 1 displayed a syndrome of general hypoplasia (fetal runting), whereas exencephaly was found in Ts 12. It was the only trisomy observed in this study that was associated with gross malformation.

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The Hodgkin's lymphoma-derived cell line L540, which exhibits multiple marker chromosomes and a genotype characteristic of T-cell origin, showed expression of MET oncogene. L540 was studied by in situ hybridization for chromosomal rearrangements concerning the regions where genes for TCRA and TCRB chains, for MET oncogene, and for rRNA are located. All four genes were demonstrated to be involved in the formation of marker chromosomes. Especially remarkable was the participation of rDNA-bearing regions in two different translocations.

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