IDENTIFICATION/CHARACTERIZATION OF POTENTIAL NOVEL MATERNAL-EFFECT GENE PRODUCTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Oocyte-derived maternal-effect proteins direct a series of crucial events occurring at the oocyte-to-embryo transition, including the completion of the second meiosis, the initiation of the first mitosis, and the activation of the embryonic genome. Few maternal-effect proteins have been identified and little is known about the mechanisms mediating their functions. The goal of this research is to identify and characterize novel potential maternal-effect genes. Using in silico subtraction, we have identified four novel genes named xw13, xw44, xw46 and xw47 in mice. Based on the spatial and temporal distribution of these mRNAs, I hypothesize that the four novel genes encode maternal effect proteins that are required for the oocyte-to-embryo transition in mice. Two specific aims are designed: Aim 1, characterization of gene products encoded by these novel genes. We will generate specific antibodies against the four novel deduced proteins to characterize their protein structure and expression in mouse tissues and early embryos, and identify their orthologs in nonhuman primates and humans; Aim 2, elucidation of the functional significance of the novel gene products in the oocyte-to-embryo transition in vitro. Applying in vitro RNAi and transgene methodologies in mouse oocytes and early embryos, we will study the potential functions of the novel gene products during oocyte maturation, fertilization, and early embryogenesis. Approximately 50% of pregnancy loss is associated with preimplantation defects in humans. Thus, the studies on maternal effect proteins will provide key insights into possible gene products that are implicated in idiopathic human infertility.