A chicken transferrin gene in transgenic mice escapes X-chromosome inactivation

Michael A. Goldman, Karen R. Stokes, Rejean L. Idzerda, G. Stanley McKnight, Robert E Hammer, Ralph L. Brinster, Stanley M. Gartler

Research output: Contribution to journalArticle

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Abstract

Mammalian X-chromosome inactivation involves a coordinate shutting down of physically linked genes. Several proposed models require the presence of specific sequences near genes to permit the spread of inactivation into these regions. If such models are correct, one might predict that heterologous genes transferred onto the X chromosome might lack the appropriate signal sequences and therefore escape inactivation. To determine whether a foreign gene inserted into the X chromosome is subject to inactivation, transgenic mice harboring 11 copies of the complete, 17-kilobase chicken transferrin gene on the X chromosome were used. Male mice hemizygous for this insert were bred with females bearing Searle's translocation, an X-chromosome rearrangement that is always active in heterozygous females (the unrearranged X chromosome is inactive). Female offspring bearing the Searle's translocation and the chicken transferrin gene had the same amount of chicken transferrin messenger RNA in liver as did transgenic male mice or transgenic female mice lacking the Searle's chromosome. This result shows that the inserted gene is not subject to X-chromosome inactivation and suggests that the inactivation process cannot spread over 187 kilobases of DNA in the absence of specific signal sequences required for inactivation.

Original languageEnglish (US)
Pages (from-to)593-595
Number of pages3
JournalScience
Volume236
Issue number4801
StatePublished - 1987

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X Chromosome Inactivation
Transferrin
Transgenic Mice
Chickens
X Chromosome
Genes
Protein Sorting Signals
Mammalian Chromosomes
X-Linked Genes
Chromosomes
Messenger RNA
Liver
DNA

ASJC Scopus subject areas

  • General

Cite this

Goldman, M. A., Stokes, K. R., Idzerda, R. L., McKnight, G. S., Hammer, R. E., Brinster, R. L., & Gartler, S. M. (1987). A chicken transferrin gene in transgenic mice escapes X-chromosome inactivation. Science, 236(4801), 593-595.

A chicken transferrin gene in transgenic mice escapes X-chromosome inactivation. / Goldman, Michael A.; Stokes, Karen R.; Idzerda, Rejean L.; McKnight, G. Stanley; Hammer, Robert E; Brinster, Ralph L.; Gartler, Stanley M.

In: Science, Vol. 236, No. 4801, 1987, p. 593-595.

Research output: Contribution to journalArticle

Goldman, MA, Stokes, KR, Idzerda, RL, McKnight, GS, Hammer, RE, Brinster, RL & Gartler, SM 1987, 'A chicken transferrin gene in transgenic mice escapes X-chromosome inactivation', Science, vol. 236, no. 4801, pp. 593-595.
Goldman MA, Stokes KR, Idzerda RL, McKnight GS, Hammer RE, Brinster RL et al. A chicken transferrin gene in transgenic mice escapes X-chromosome inactivation. Science. 1987;236(4801):593-595.
Goldman, Michael A. ; Stokes, Karen R. ; Idzerda, Rejean L. ; McKnight, G. Stanley ; Hammer, Robert E ; Brinster, Ralph L. ; Gartler, Stanley M. / A chicken transferrin gene in transgenic mice escapes X-chromosome inactivation. In: Science. 1987 ; Vol. 236, No. 4801. pp. 593-595.
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abstract = "Mammalian X-chromosome inactivation involves a coordinate shutting down of physically linked genes. Several proposed models require the presence of specific sequences near genes to permit the spread of inactivation into these regions. If such models are correct, one might predict that heterologous genes transferred onto the X chromosome might lack the appropriate signal sequences and therefore escape inactivation. To determine whether a foreign gene inserted into the X chromosome is subject to inactivation, transgenic mice harboring 11 copies of the complete, 17-kilobase chicken transferrin gene on the X chromosome were used. Male mice hemizygous for this insert were bred with females bearing Searle's translocation, an X-chromosome rearrangement that is always active in heterozygous females (the unrearranged X chromosome is inactive). Female offspring bearing the Searle's translocation and the chicken transferrin gene had the same amount of chicken transferrin messenger RNA in liver as did transgenic male mice or transgenic female mice lacking the Searle's chromosome. This result shows that the inserted gene is not subject to X-chromosome inactivation and suggests that the inactivation process cannot spread over 187 kilobases of DNA in the absence of specific signal sequences required for inactivation.",
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AU - Brinster, Ralph L.

AU - Gartler, Stanley M.

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N2 - Mammalian X-chromosome inactivation involves a coordinate shutting down of physically linked genes. Several proposed models require the presence of specific sequences near genes to permit the spread of inactivation into these regions. If such models are correct, one might predict that heterologous genes transferred onto the X chromosome might lack the appropriate signal sequences and therefore escape inactivation. To determine whether a foreign gene inserted into the X chromosome is subject to inactivation, transgenic mice harboring 11 copies of the complete, 17-kilobase chicken transferrin gene on the X chromosome were used. Male mice hemizygous for this insert were bred with females bearing Searle's translocation, an X-chromosome rearrangement that is always active in heterozygous females (the unrearranged X chromosome is inactive). Female offspring bearing the Searle's translocation and the chicken transferrin gene had the same amount of chicken transferrin messenger RNA in liver as did transgenic male mice or transgenic female mice lacking the Searle's chromosome. This result shows that the inserted gene is not subject to X-chromosome inactivation and suggests that the inactivation process cannot spread over 187 kilobases of DNA in the absence of specific signal sequences required for inactivation.

AB - Mammalian X-chromosome inactivation involves a coordinate shutting down of physically linked genes. Several proposed models require the presence of specific sequences near genes to permit the spread of inactivation into these regions. If such models are correct, one might predict that heterologous genes transferred onto the X chromosome might lack the appropriate signal sequences and therefore escape inactivation. To determine whether a foreign gene inserted into the X chromosome is subject to inactivation, transgenic mice harboring 11 copies of the complete, 17-kilobase chicken transferrin gene on the X chromosome were used. Male mice hemizygous for this insert were bred with females bearing Searle's translocation, an X-chromosome rearrangement that is always active in heterozygous females (the unrearranged X chromosome is inactive). Female offspring bearing the Searle's translocation and the chicken transferrin gene had the same amount of chicken transferrin messenger RNA in liver as did transgenic male mice or transgenic female mice lacking the Searle's chromosome. This result shows that the inserted gene is not subject to X-chromosome inactivation and suggests that the inactivation process cannot spread over 187 kilobases of DNA in the absence of specific signal sequences required for inactivation.

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