Transgenic RNAi-mediated reduction of MSY2 in mouse oocytes results in reduced fertility

Dev Biol. 2004 Apr 1;268(1):195-206. doi: 10.1016/j.ydbio.2003.12.020.


MSY2 is implicated in regulating the stability and translation of maternal mRNAs during mouse oogenesis. We report here that by driving the expression of a transgene encoding an Msy2 hairpin dsRNA in growing oocytes using the oocyte-specific Zp3 promoter, the amount of MSY2 protein was reduced by at least 60% in fully grown oocytes. The decrease appeared specific because no decrease was observed in either non-targeted mRNAs or proteins. Fertility of transgenic females was severely reduced. Although transgenic eggs could be inseminated, the eggs did not exhibit the normal series of oscillations in intracellular Ca2+, resume meiosis, undergo cortical granule exocytosis, or ZP2 cleavage to ZP2f. Transgenic oocytes also displayed a higher incidence of both the non-surrounded nucleolus chromatin morphology, and abnormal meiotic spindle formation was observed following oocyte maturation. Transgenic oocytes contained less total mRNA (approximately 75-80% that of non-transgenic oocytes) and displayed a reduced level of protein synthesis. Moreover, several of the maturation-associated changes in protein synthesis failed to occur in the transgenic oocytes. These results support a role for MSY2 in stabilizing maternal mRNAs in growing oocytes, a process essential to generate meiotically and developmentally competent oocytes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers
  • Female
  • Fertility / genetics*
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Oocytes / metabolism*
  • RNA, Antisense / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism


  • DNA Primers
  • RNA, Antisense
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Ybx2 protein, mouse