PgmNr M5065: Role of a 3’UTR-dependent DAZL suppression in mouse postnatal ovary.

Authors:
K. Fukuda 1 ; T. Naka 3 ; A. Suzuki 3 ; Y. Saga 1,2 ; Y. Kato 1,2


Institutes
1) SOKENDAI, Mishima, JP; 2) NIG,Mishima, JP; 3) Yokohama national Univ., Yokohama, JP.


Abstract:

Oogenesis is a crucial process for producing healthy female gamete, oocyte, in ovary. One of essential genes for oogenesis is Dazl (deleted in azoospermia-like) that is an RNA-binding protein implicated in translational promotion in mice. Because of its indispensable role in progression of meiosisⅠ in embryonic gonads and in progression of meiosisⅡ after ovulation‚ Dazl is thought to be required throughout oogenesis. However, its role in oocyte growth in postnatal ovary remains unknown. To address this question, we analyzed Dazl expression by qPCR and western blotting. Surprisingly, we found that DAZL protein was decreased in postnatal ovaries, whereas the higher level of Dazl mRNA was maintained from embryo to juvenile ovaries. These results indicate that DAZL is post-transcriptionally suppressed after birth. We asked whether or not Dazl is suppressed via its 3’UTR in ovary. To investigate this hypothesis, we asked whether Dazl translation is suppressed via its 3’UTR or not by analyzing a bacterial artificial chromosome (BAC) carrying transgenic mouse line in which the Dazl 3’-UTR was flanked with Frt sequences followed by rabbit β-globin 3’-UTR. We crossed the BAC transgenic mice to Gt(ROSA)26Sortm2(FLP*)Sor (Rosa-Flp) mice to remove the Dazl 3’-UTR and investigated the DAZL expression. The results showed that DAZL expression was increased when the 3’–UTR was removed‚ suggesting that Dazl translation is suppressed in a 3’–UTR–dependent manner. In order to investigate the effect of excess DAZL on female reproduction‚ we examined the litter size of transgenic females. Interestingly, female mice expressing excess DAZL produced reduced number of offspring. These data indicate that 3’UTR–dependent suppression of DAZL in postnatal oocytes is important for female reproduction. These data also indicate the presence of a mechanism to suppress DAZL expression in the 3’UTR dependent manner.