PARENT SESSION

(134) ROLE OF MIXED LINEAGE LEUKEMIA 2 (MLL2) ON FERTILITY AND EARLY EMBRYONIC DEVELOPMENT.

Andreu-Vieyra, Claudia¹, Agno, Julio¹, Stewart, Francis², Matzuk, Martin¹, ¹ Baylor College of Medicine, Houston, TX² Biotec, Technische Universitat Dresden, Dresden, Germany

ABSTRACT- In the mouse, the major wave of embryonic gene activation occurs at the 2-cell stage. The oocyte-embryo transition is therefore dependent on maternal transcripts and proteins stored during oogenesis (maternal-effect gene products). Reprogramming of gene expression also occurs during the transition of maternal to zygotic transcription, likely by changes in chromatin structure. To date, however, few genes essential for the early stages of development have been characterized. During early embryogenesis, the trithorax group (trx-G) family of proteins has a role in the maintenance of homeotic gene expression and transcriptional activation. Importantly, some members of the trx-G family have been shown to be stored as maternal factors. We are investigating the role of MLL2/ALR, a trx-G family member, on ovarian function and early embryonic development under the hypotheses that MLL2 functions in both ovarian granulosa cells and the oocyte to regulate folliculogenesis and as a maternal-effect protein, respectively. To test these hypotheses we are using both conditional knockout mice and a hypomorphic mouse model. In fertility studies, females that were hypomorphic for MLL2 were shown to be infertile. To investigate the origin of this infertility, ovaries, oocytes, and embryos were collected for histological analysis, as well as cell cultures and immunostaining. Ovarian defects, oocyte maturation defects, and an embryonic developmental block were observed in the mutant females. Immunostaining analysis of embryos revealed that abnormal chromatin remodeling might be partially responsible for the observed embryonic developmental arrest. We are further evaluating these abnormalities in the conditional knockout model. Overall, our results suggest that MLL2 is a maternal effect gene and an important transcriptional regulator during early embryogenesis.

KEY WORDS: MLL2, embryogenesis, fertility, maternal effect gene