The mouse polyubiquitin gene Ubb is essential for meiotic progression.
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.
Ryu
Kwon-Yul
KY
Department of Biological Sciences, Bio-X Program, Stanford University, Stanford, California 94305, USA.
Sinnar
Shamim A
SA
Reinholdt
Laura G
LG
Vaccari
Sergio
S
Hall
Susan
S
Garcia
Manuel A
MA
Zaitseva
Tatiana S
TS
Bouley
Donna M
DM
Boekelheide
Kim
K
Handel
Mary Ann
MA
Conti
Marco
M
Kopito
Ron R
RR
D000818:Animals; D005075:Biological Evolution; D005260:Female; D005854:Germ Cells / Q000166:cytology*; D007246:Infertility / Q000209:etiology; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D025821:Polyubiquitin / Q000235:genetics / Q000502:physiology*; D025801:Ubiquitin / Q000502:physiology*
C527284:Ubb protein, mouse; D025801:Ubiquitin; D025821:Polyubiquitin