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Inactivation of the Rps4 gene on the mouse X chromosome
A R Zinn1, S L Bressler, P Beer-Romero
1Howard Hughes Research Laboratories, Whitehead Institute, Cambridge, Massachusetts.
Abstract:
The human RPS4X and RPS4Y genes, located on the X and Y chromosomes, appear to encode isoforms of ribosomal protein S4. Haploinsufficiency of these genes may contribute to the human phenotype known as Turner syndrome. Although RPS4X maps near the X-inactivation center, the gene is expressed on inactive human X chromosomes. We cloned Rps4, the mouse homolog of RPS4X. Exploiting allelic variation in Rps4, we examined transcription of the gene from active and inactive mouse X chromosomes in vivo, in female mice carrying an X-autosome translocation. We report that mouse Rps4, unlike human RPS4X, is subject to X inactivation. This finding may explain, at least in part, why the phenotypic consequences of X monosomy are less severe in mice than in humans.
Insights
Mouse Rps4 is subject to X inactivation, unlike human RPS4X. This difference in X inactivation may explain why X monosomy is less severe in mice than in humans, impacting Turner syndrome research.
Area of Science:
- Genetics
- Developmental Biology
- Molecular Biology
Background:
- The human RPS4X and RPS4Y genes encode ribosomal protein S4 isoforms.
- Haploinsufficiency of these genes is implicated in Turner syndrome.
- Human RPS4X escapes X inactivation despite its proximity to the X-inactivation center.
Purpose of the Study:
- To investigate the X inactivation status of the mouse Rps4 gene, the homolog of human RPS4X.
- To compare the X inactivation behavior of mouse Rps4 with human RPS4X.
- To understand the genetic basis for differential severity of X monosomy phenotypes between mice and humans.
Main Methods:
- Cloned the mouse Rps4 gene.
- Utilized allelic variation in Rps4 for experimental tracking.
- Examined Rps4 gene transcription from active and inactive X chromosomes in vivo using female mice with an X-autosome translocation.
Main Results:
- Mouse Rps4 is subject to X inactivation.
- Human RPS4X escapes X inactivation.
- Demonstrated differential regulation of homologous genes between species.
Conclusions:
- Mouse Rps4 undergoes X inactivation, contrasting with human RPS4X.
- This difference in X inactivation may contribute to the milder phenotype of X monosomy in mice compared to humans.
- Provides insights into species-specific gene regulation and its impact on developmental disorders.