Rad51 Conditional Knockout mouse models

Strand invasion during homologous recombination is executed by RAD51, and Rad51 is the mouse ortholog of human RAD51, encoding the RecA-family recombinase that displaces RPA from resected single-stranded DNA with BRCA2 BRC repeat assistance, polymerizes into an ATP-dependent helical nucleoprotein filament, searches the sister chromatid for homology and catalyzes D-loop formation. Beyond recombination, RAD51 coats and protects stalled replication forks from MRE11 and DNA2 degradation, a function genetically separable from strand exchange. Germline deletion causes very early embryonic lethality that Trp53 loss only partially delays, so conditional nulls with inducible Cre are essential for adult analysis, while dominant-negative Walker motif mutants such as K133R or K133A permit acute, reversible interference with filament turnover. Because the paralogs RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3 act as mediators rather than substitutes, they cannot rescue loss; match allele class to whether the endpoint is repair capacity, fork protection or chemosensitivity.

Tissue restricted knockout of Rad51 keeps wild type function everywhere else. Breeding is often more robust, and the setup mirrors patient biology where mutations arise in a subset of cells.