Fertile offspring from sterile sex chromosome trisomic mice
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Takayuki Hirota Hiroshi Ohta Benjamin Powell Shantha Mahadevaiah Andrew Ojarikre Mitinori Saitou James TurnerAbstract
Having the correct number of chromosomes is vital for normal development and health. Sex chromosome trisomy (SCT) affects 0.1% of the human population and is associated with infertility. We show that during reprogramming to induced pluripotent stem cells (iPSC), fibroblasts from sterile trisomic XXY and XYY mice lose the extra sex chromosome, by a phenomenon we term trisomy-biased chromosome loss (TCL). Resulting euploid XY iPSCs can be differentiated into the male germ cell lineage and functional sperm that can be used in intracytoplasmic sperm injection to produce chromosomally normal, fertile offspring. Sex chromosome loss is comparatively infrequent during mouse XX and XY iPSC generation. TCL also applies to other chromosomes, generating euploid iPSCs from cells of a Down syndrome mouse model. It can also create euploid iPSCs from human trisomic patient fibroblasts. The findings have relevance to overcoming infertility and other trisomic phenotypes.
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Journal Science
Volume 357
Issue number 6354
Pages 932-935
Available online
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Publisher website (DOI) 10.1126/science.aam9046
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Europe PubMed Central 28818972
Pubmed 28818972
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