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Loss- and Gain-of-function Approach to Investigate Early Cell Fate Determinants in Preimplantation Mouse Embryos
Published on: June 6, 2016
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XRCC3 loss leads to midgestational embryonic lethality in mice
Rohit Prakash1, Laina Freyer2, Néstor Saiz3
1Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 430 East 67 Street, New York, NY 10065, United States; Regeneron Pharmaceuticals, Tarrytown, New York, NY, United States.
DNA Repair
|October 3, 2021
Summary
Mice lacking XRCC3, a key DNA repair protein, experience mid-gestational lethality due to developmental abnormalities. This highlights the essential role of XRCC3 and RAD51 paralog complexes in mouse development and genome integrity.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- RAD51 paralogs are crucial for homologous recombination (HR) DNA repair.
- Previous mouse studies reported embryonic lethality for four RAD51 paralogs.
- The developmental role of the XRCC3 RAD51 paralog was previously unknown.
Purpose of the Study:
- To investigate the in vivo function of XRCC3 in mouse development.
- To determine the consequences of XRCC3 deficiency on embryonic development.
- To assess the necessity of XRCC3-containing RAD51 paralog complexes for embryogenesis.
Main Methods:
- Generation and analysis of Xrcc3 knockout mice.
- Characterization of embryonic phenotypes at various gestational stages.
- Assessment of developmental abnormalities and lethality.
- Analysis of Xrcc3 knockin mutants and Trp53 interactions.
Main Results:
- Xrcc3 knockout mice exhibit mid-gestational embryonic lethality.
- Deficiencies in XRCC3 lead to developmental abnormalities, including small size and failure to turn.
- A catalytically inactive XRCC3 mutant also causes embryonic lethality.
- Trp53 mutations can partially rescue the lethality, indicating XRCC3's role in genome integrity.
Conclusions:
- XRCC3 is essential for mouse embryonic development.
- Both RAD51 paralog complexes, including the one containing XRCC3 and RAD51C, are required for embryogenesis.
- XRCC3 plays a critical role in maintaining genome integrity during development.
