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Transgenic mice carrying an Xist-containing YAC
E Heard1, C Kress, F Mongelard
1Unité de Génétique Moléculaire Murine, Institut Pasteur, Paris, France.
Human Molecular Genetics
|April 1, 1996
Summary
Researchers investigated the X-inactivation centre (Xic) in female mammals. Transgenic mice carrying a large DNA region including the Xist gene did not initiate X-chromosome inactivation, suggesting key sequences are missing.
Area of Science:
- Genetics
- Mammalian development
- Epigenetics
Background:
- X-chromosome inactivation (XCI) is crucial for dosage compensation in female mammals.
- The X-inactivation centre (Xic) on the X chromosome controls this process.
- The Xist gene, located within the Xic, is essential for initiating XCI and is expressed from the inactive X chromosome.
Purpose of the Study:
- To determine if a large genomic region encompassing the Xist gene from the Xic can initiate X-chromosome inactivation.
- To test the sufficiency of the Xist gene and surrounding sequences for XCI initiation.
Main Methods:
- Creation of transgenic mice using a 460 kb yeast artificial chromosome (YAC) containing the Xic region and Xist gene.
- Analysis of Xist gene expression in the transgenic mice.
- Monitoring of a LacZ reporter gene and two endogenous genes normally silenced on the inactive X chromosome.
Main Results:
- Transgenic mice did not show initiation of X-chromosome inactivation.
- Expression of Xist and reporter genes was not as expected for XCI.
- Analysis suggests that essential sequences for Xist expression and XCI initiation may be absent in the YAC construct.
Conclusions:
- The tested 460 kb YAC containing Xist and flanking regions is insufficient to initiate X-chromosome inactivation.
- Further investigation is needed to identify all essential elements within the Xic required for XCI.
- This study highlights the complexity of XCI regulation and the potential for missing regulatory elements in large genomic constructs.