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

Abstract

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.

Developmental Abnormalities in Mouse Embryos Tetrasomic for Chromosome 11: Apparent Similarity to Embryos Functionally Disomic for the X Chromosome.

“…Female mice homozygous for Rb(10.11)8Bnr (shortened hereafter to Rb8) (Gropp et al, 1972) were mated with males homozygous for Rb(11.13)6Lub (shortened hereafter to Rb6) (Capanna et al, 1976) or vice versa. F1 mice doubly heterozygous for these translocations (which are thus characterized by monobrachial homology for chromosome 11) were mated to produce embryos trisomic or tetrasomic for chromosome 11 taking advantage of the high frequency of meiotic nondisjunction in such mice (Gropp et al, 1975;White et al, 1972). Fig.…”

“…Production of mouse embryos having 0 to 4 copies of chromosome 11 by mating Rb8 and Rb6 stock mice (Gropp et al, 1972;Capanna et al, 1976). F1 mice doubly heterozygous for both translocations (which are thus characterized by monobrachial homology for chromosome 11) were mated to produce embryos trisomic or tetrasomic for chromosome 11 taking advantage of the high frequency of meiotic nondisjunction in such mice (Gropp et al, 1975). Only the three pairs of chromosomes involved in the metacentrics are shown here.…”

“…The availability of mouse stocks having various Robertsonian translocations (Beechey and Evans, 1996) has facilitated systematic studies of the developmental effects of increases or decreases in the copy number of a specific autosome (Gropp et al, 1974(Gropp et al, , 1975. Embryos trisomic for any autosome survive at least until midgestation, although the stage of lethality varies widely among different chromosomes (Epstein, 1986).…”

Meiotic Nondisjunction in the Mouse: Methodology for Genetic Testing and Comparison with Other Methods

“…In the second scheme, any + + progeny would be potentially trisomic for the marked chromosome and could be distinguished from a recombinant by a chromosome count. By "manufacturing" trisomics' from matings involving Robertsonian translocations in the mouse (54,55), it has now been shown for many chromosomes that the trisomic condition is lethal between midgestation and the day of birth, depending on the chromosome involved. Therefore, any marker genes used would have to be expressed and readily detectable during this interval, and, as of now, not enough such markers are available to tag more than a very few chromosomes.…”

Effects of genetic background on cardiovascular anomalies in the Ts16 mouse

“…However, mouse models that have been developed for the study of DS provide a useful tool for looking at the effect of background genotype on specific components of an aneuploid phenotype. Mouse trisomy 16 (Ts16) was one of the first such models to be developed (Gropp et al, 1975;Cox et al, 1984).Although Ts16 is no longer used as a model for DS, its robust phenotype makes it an attractive subject for the investigation of the effects of genetic background on phenotype. Here, we explore the effects of four different genetic backgrounds on the phenotype of Ts16 embryos and fetuses.…”