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Updated: Aug 14, 2026
Mouse Genome Engineering Using Designer Nucleases
Published on: April 2, 2014
Mouse Ubc9 knockout: many path(way)s to ruin
1Laboratory of Protein Dynamics and Signaling, National Cancer Institute, NCI-Frederick, Frederick, Maryland 21702, USA.
Abstract:
In this issue of Developmental Cell, Nacerddine et al. (2005) describe a targeted germ line mutation of the mouse SUMO-specific E2 Ubc9, which abrogates the SUMO conjugation pathway, broadly crippling nuclear function in proliferating cells of the early embryo. This study reveals the wide-ranging roles for this protein modifier in nuclear organization, chromosome segregation, and Ran-driven nucleo-cytoplasmic transport.
Insights
Researchers disrupted the Ubc9 gene, essential for SUMOylation, in mice. This disruption crippled nuclear functions in early embryonic cells, impacting key processes like chromosome segregation.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cell Biology
Background:
- SUMOylation is a crucial post-translational modification regulating various cellular processes.
- The SUMO-specific E2 enzyme Ubc9 plays a central role in the SUMO conjugation pathway.
- Understanding Ubc9's function is vital for comprehending nuclear organization and cell proliferation.
Purpose of the Study:
- To investigate the in vivo function of Ubc9 in early mouse embryonic development.
- To elucidate the impact of abrogating the SUMO conjugation pathway on nuclear functions.
- To identify the specific roles of Ubc9 in processes such as chromosome segregation and nucleo-cytoplasmic transport.
Main Methods:
- Generation of a targeted germ line mutation in the mouse Ubc9 gene.
- Analysis of embryonic lethality and developmental defects.
- Assessment of nuclear organization, chromosome segregation, and nucleo-cytoplasmic transport in mutant cells.
Main Results:
- Targeted mutation of Ubc9 abrogated the SUMO conjugation pathway in early embryos.
- Loss of Ubc9 function led to widespread nuclear dysfunction in proliferating embryonic cells.
- Defects were observed in nuclear organization, chromosome segregation, and Ran-driven nucleo-cytoplasmic transport.
Conclusions:
- Ubc9 is essential for normal nuclear function and embryonic development in mice.
- The SUMO conjugation pathway, mediated by Ubc9, plays critical roles in maintaining genome stability and nuclear transport.
- This study highlights the broad impact of Ubc9 on fundamental cellular processes during early development.
