The Mouse Polyubiquitin Gene Ubb Is Essential for Meiotic Progression

Abstract

ABSTRACT Ubiquitin is encoded in mice by two polyubiquitin genes, Ubb and Ubc , that are considered to be stress inducible and two constitutively expressed monoubiquitin ( Uba ) genes. Here we report that targeted disruption of Ubb results in male and female infertility due to failure of germ cells to progress through meiosis I and hypogonadism. In the absence of Ubb , spermatocytes and oocytes arrest during meiotic prophase, before metaphase of the first meiotic division. Although cellular ubiquitin levels are believed to be maintained by a combination of functional redundancy among the four ubiquitin genes, stress inducibility of the two polyubiquitin genes, and ubiquitin recycling by proteasome-associated isopeptidases, our results indicate that ubiquitin is required for and consumed during meiotic progression. The striking similarity of the meiotic phenotype in Ubb −/− germ cells to the sporulation defect in fission yeast ( Schizosaccharomyces pombe ) lacking a polyubiquitin gene suggests that a meiotic role of the polyubiquitin gene has been conserved throughout eukaryotic evolution.