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

X chromosome inactivation is initiated from a segment of the mammalian X ch romosome called the X inactivation center. Transgenes from this region of t he murine X chromosome are providing the means to identify the DNA needed f or 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; similar to6 copies of a 480-kb h uman transgene (ES-10) were sufficient to initiate random X inactivation in cells of male chimeric mice (Migeon ct at, 1999, Genomics, 59, 113-121), N ow, we report studies of another human transgene (ES-5), which contains les s than 300 kb of the human XIC region on Xq13.2 including an intact XIST lo cus and which has inserted in one or two copies into mouse chromosome 6. Th e ES-5 transgene is recognized as an X inactivation center in mouse embryon ic stem cells, but is not sufficient to induce random X inactivation in som atic cells of highly chimeric mice. Human transgenes in chimeric mice provi de a means to uncouple the key steps in this complex pathway and facilitate the search for essential components of the human XIC region. (C) 2001 Acad emic Press.