Low level chromosome instability in embryonic cells of primary aneuploid mice.
Karyotypic analyses of Down syndrome patients have identified a low level of chromosome mosaicism, suggesting that the primary aneuploid status of the cells promotes further chromosomal segregation errors. Sycp3-null female mice produce aneuploid oocytes, which after fusion with normal haploid sperm, result in offspring with systemic whole chromosome, aneuploid embryo cells. Using the Sycp3-null female as a model, we observe an increase in the number of embryonic cells at E7.0 that exhibit abnormal chromosomal bridges at the anaphas estage of mitosis. This result suggests that global changes in gene expression patterns resulting from primary aneuploidy can affect mitotic chromosome segregation, resulting in a low level of chromosomal instability. The increased level of chromosomal instability could in the absence of mitotic checkpoints, lead to chromosomal mosaicism within the adult organism, as seen in Down syndrome patients.
Department of Cell and Molecular Biology and Center for Genomics and Bioinformatics, Karolinska Institutet, Stockholm, Sweden.
D A
DA
Lightfoot
C
C
Höög
D000782:Aneuploidy; D000818:Animals; D043171:Chromosomal Instability / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004622:Embryo, Mammalian / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains