TY - JOUR
T1 - 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
AU - Migeon, Barbara R.
AU - Winter, Holly
AU - Kazi, Ethan
AU - Chowdhury, Ashis K.
AU - Hughes, Aisha
AU - Haisley-Royster, Camille
AU - Morrison, Harris
AU - Jeppesen, Peter
N1 - Funding Information:
We thank Drs. Roger Reeves for his helpful suggestions, Bryan Turner for R5/12 antiserum, Ethylin Wang Jabs for advice during preparation of the manuscript, and Rick Tracy for his contributions to the figures. This work was supported by NICHD Grant HD05465.
PY - 2001/1/15
Y1 - 2001/1/15
N2 - 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.
AB - 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.
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U2 - 10.1006/geno.2000.6421
DO - 10.1006/geno.2000.6421
M3 - Article
C2 - 11161809
AN - SCOPUS:0035862543
SN - 0888-7543
VL - 71
SP - 156
EP - 162
JO - Genomics
JF - Genomics
IS - 2
ER -