Chromosome stability differs in cloned mouse embryos and derivative ES cells.
The mechanisms that have evolved to maintain genome stability during cell cycle progression are challenged when a somatic cell nucleus is placed in a meiotic environment such as the ooplasm. Chromosomal spindle aberrations ensue in the majority of reconstructed oocytes within 2 h of transplantation, but it is not known if they recover or persist with the onset of embryonic divisions. We analyzed the chromosomal spindles and the karyotype of cumulus cell-derived mouse clones through the initial and hence most critical mitoses. Cloned embryos start out with less aneuploidy than fertilized embryos but surpass them after ES cell derivation, as measured by frequencies of chromosome trisomies and structural rearrangements. Despite the limited proportion of cloned mouse embryos that reach late gestation, a phenotypic mutation lacking a karyotypic mark was found in a newborn mouse cloned in 2002 and has been inherited since by its offspring. These data concur with a prevalent epigenetic, rather than genetic, basis for cloned embryo failure, but they also warn against the temptation to think that all conditions of clones are epigenetic and recover during gametogenesis. The cloning procedure is defenseless (no matter how technically refined) towards pre-existing or induced subchromosomal mutations that are below the experimental detection limit of the cytogenetic assay.
Balbach
Sebastian T
ST
Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany.
Jauch
Anna
A
Böhm-Steuer
Barbara
B
Cavaleri
Fatima M
FM
Han
Yong-Mahn
YM
Boiani
Michele
M
D000782:Aneuploidy; D000818:Animals; D043171:Chromosomal Instability; D019976:Cloning, Organism; D053595:Embryonic Stem Cells / Q000648:ultrastructure*; D044127:Epigenesis, Genetic; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D007621:Karyotyping; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation; D053652:Nuclear Transfer Techniques; D010641:Phenotype; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic; D008941:Spindle Apparatus / Q000648:ultrastructure