Fertility is compromised after oocyte-specific deletion of microtubule severing protein Katanin A1.

Katanins are microtubule severing enzymes that play roles in diverse cell functions including meiotic and mitotic spindle formation. To address the role of Katanin p60 isozymes in mammalian oocytes, we have used the ZP3-CreLox approach to specifically delete Katanin A1 (KATNA1) and Katanin A-like 1 (KATNAL1) from the start of oocyte growth. Here, we show that KATNAL1 is not required for normal fertility, but deletion of KATNA1 causes a 50% decrease in fertility. Further investigation in Katna1-/- oocytes revealed no effect on MI spindle morphology but a modest effect on the morphology of MII spindles. This was accompanied by a decreased rate of fertilization, but Katna1-/+ heterozygous embryos that reached the 2-cell stage developed at normal rates to the blastocyst stage. Parthenogenetic activation of Katna1-/- oocytes to generate diploid homozygous embryos revealed a reduced rate of blastocyst formation. Further, the Katna1-/- parthenogenetic blastocysts had a reduced diameter, decreased cell number, and increased nuclear size. Taken together, our data indicate KATNA1, but not KATNAL1, plays a role in MII spindle function and mitotic cell divisions of the preimplantation embryo. The ability of the paternal allele to rescue preimplantation development suggests the origin of the decrease in the fertility of conditional Katna1-/- mice lies in abnormalities arising in the egg to embryo transition prior to embryonic genome activation.