Document Type


Publication Date




JAX Source

Sci Adv 2020 Oct 23; 6(43):eabb6606





JAX Scholar Award, HD007065,GM99640,HD093778,GM125736,CA034196


In many mammals, genomic sites for recombination are determined by the histone methyltransferase PRMD9. Some mouse strains lacking PRDM9 are infertile, but instances of fertility or semifertility in the absence of PRDM9 have been reported in mice, canines, and a human female. Such findings raise the question of how the loss of PRDM9 is circumvented to maintain fertility. We show that genetic background and sex-specific modifiers can obviate the requirement for PRDM9 in mice. Specifically, the meiotic DNA damage checkpoint protein CHK2 acts as a modifier allowing female-specific fertility in the absence of PRDM9. We also report that, in the absence of PRDM9, a PRDM9-independent recombination system is compatible with female meiosis and fertility, suggesting sex-specific regulation of meiotic recombination, a finding with implications for speciation.


This paper is dedicated to the memory of Kenneth Paigen, a visionary, a beloved colleague, and a great mentor. We thank three anonymous reviewers for helpful comments. We thank J. Eppig and all members of the Bolcun-Filas, Handel, Paigen, and Petkov labs for insightful discussions and suggestions. We acknowledge the expertise and contributions of The Jackson Laboratory Scientific Services, including the Histology core, the Microscopy core, Genome Technologies, Genetic Engineering Technology, and Mouse Resources for expertise and help during this project. We thank the Knockout Mouse Project (KOMP2) at The Jackson Laboratory for providing mice. We thank A. Toth, P. Cohen, and N. Hunter for sharing antibody resources.