biostudies-literaturePrakash RNICHD NIH HHSNCINIDDK NIH HHSNCI NIH HHSNational Institutes of Health103227https://www.ebi.ac.uk/biostudies/studies/S-EPMC8783620biostudies-literatureUnknown108RAD51 paralogs are key components of the homologous recombination (HR) machinery. Mouse mutants have been reported for four of the canonical RAD51 paralogs, and each of these mutants exhibits embryonic lethality, although at different gestational stages. However, the phenotype of mice deficient in the fifth RAD51 paralog, XRCC3, has not been reported. Here we report that Xrcc3 knockout mice exhibit midgestational lethality, with mild phenotypes beginning at about E8.25 but severe developmental abnormalities evident by E9.0-9.5. The most obvious phenotypes are small size and a failure of the embryo to turn to a fetal position. A knockin mutation at a key ATPase residue in the Walker A box results in embryonic lethality at a similar stage. Death of knockout mice can be delayed a few days forDNA repairXRCC3 loss leads to midgestational embryonic lethality in mice.PMC8783620R01DK127821R01HD086478P30 CA008748R01 DK127821R35CA253174P30CA008748R01 HD086478R35 CA253174R01 HD094868R01HD094868Freyer LGavrilov SPrakash RRomanienko PJLacy ESaiz NJasin MHadjantonakis AKWang RQfalseXRCC3 loss leads to midgestational embryonic lethality in mice.RAD51 paralogs are key components of the homologous recombination (HR) machinery. Mouse mutants have been reported for four of the canonical RAD51 paralogs, and each of these mutants exhibits embryonic lethality, although at different gestational stages. However, the phenotype of mice deficient in the fifth RAD51 paralog, XRCC3, has not been reported. Here we report that Xrcc3 knockout mice exhibit midgestational lethality, with mild phenotypes beginning at about E8.25 but severe developmental abnormalities evident by E9.0-9.5. The most obvious phenotypes are small size and a failure of the embryo to turn to a fetal position. A knockin mutation at a key ATPase residue in the Walker A box results in embryonic lethality at a similar stage. Death of knockout mice can be delayed a few days for2021-01-01T00:00:00Z2021 Dec2025-04-05T09:43:36.573Z2025-04-05T09:43:36.573ZS-EPMC87836203460138210.1016/j.dnarep.2021.103227