Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Dynamin 2 is essential for mammalian oocyte growth and function (#103)

Janet E Holt 1 , Kate Redgrove 1 , Lisa Mitchell 1 , Bettina Mihalas 1 , Adam McCluskey 1 , Eileen McLaughlin 1 , Brett Nixon 1
  1. University Of Newcastle, CALLAGHAN, NSW, Australia

The dynamin (Dnm) family are a group of GTPases best known for their roles in membrane fission and fusion events such as endocytosis, as well as in the regulation of cytoskeletal components. A role for Dnm 1/2 has recently been identified during the acrosome reaction in spermatozoa, however little is known about Dnm function in the oocyte. We have examined the expression profiles of the 3 mammalian Dnm genes (Dnm 1,2 and 3) in the mouse ovary and mature oocyte/MII egg, and identified Dnm2 as the most abundantly expressed dynamin. To determine the consequences of Dnm2 loss in oocytes, we created an oocyte-specific Dnm2 mouse knockout, (ZP3Cre;Dnm2 lox/lox). Dnm2 knockout animals failed to form follicles beyond the preantral stage, consistent with an essential housekeeping role for Dnm2 during this phase of rapid oocyte growth. To examine Dnm2 function in mature oocytes and eggs, we have employed the use of novel, small chemical modulators of Dnm activity which target different aspects of its function, combined with knockdown strategies. We find that Dnm2 is an important regulator of Meiosis I and II, with distinct functional domains of the protein conferring specific roles. Our studies indicate Dnm2 is essential for oocyte function throughout postnatal development, and sheds new light on how this protein regulates the fidelity of the 2 meiotic divisions.