Low-Copy-Number Human Transgene Is Recognized as an X Inactivation Center in Mouse ES Cells, but Fails to Induce cis-Inactivation in Chimeric Mice

• Published in: Genomics (San Diego, Calif.) Vol. 71; no. 2; pp. 156 - 162
• Main Authors: Migeon, Barbara R., Winter, Holly, Kazi, Ethan, Chowdhury, Ashis K., Hughes, Aisha, Haisley-Royster, Camille, Morrison, Harris, Jeppesen, Peter
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.01.2001; Elsevier
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Chimera - genetics; Clone Cells; Dosage Compensation, Genetic; Embryo, Mammalian - cytology; Female; Fetal Death - genetics; Fundamental and applied biological sciences. Psychology; Gene Dosage; Genes. Genome; Humans; Male; Mice; Mice, Transgenic; Molecular and cellular biology; Molecular genetics; RNA - metabolism; RNA, Long Noncoding; RNA, Untranslated - genetics; Stem Cells - metabolism; Transcription Factors - genetics; Transfection; Transgenes - genetics; X chromosome inactivation center; XIC gene; Human; Stem cell; Rodentia; Transgenic animal; Chromosome 6; Gene expression; Inactivation; Vertebrata; Mammalia; Gene; Mouse; Embryonic cell; X-Chromosome
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.2000.6421

X chromosome inactivation is initiated from a segment of the mammalian X chromosome called the X inactivation center. Transgenes from this region of the murine X chromosome are providing the means to identify the DNA needed for cis inactivation in mice. We recently showed that chimeric mice carrying transgenes from the human X inactivation center (XIC) region also provide a functional assay for human XIC activity; ∼6 copies of a 480-kb human transgene (ES-10) were sufficient to initiate random X inactivation in cells of male chimeric mice (Migeon et al., 1999, Genomics, 59, 113–121). Now, we report studies of another human transgene (ES-5), which contains less than 300 kb of the human XIC region on Xq13.2 including an intact XIST locus and which has inserted in one or two copies into mouse chromosome 6. The ES-5 transgene is recognized as an X inactivation center in mouse embryonic stem cells, but is not sufficient to induce random X inactivation in somatic cells of highly chimeric mice. Human transgenes in chimeric mice provide a means to uncouple the key steps in this complex pathway and facilitate the search for essential components of the human XIC region.