Identification and characterization of formin-2, a gene required for meiosis in the oocyte.

摘要

The Formin Homology (FH) family is comprised of proteins with similarity to formin, a protein crucial for proper limb and kidney development. The FH protein family has grown in the past decade to encompass a number of proteins found throughout evolution, from yeast to humans, which appear to function in the organization of the cytoskeleton. Many of these proteins appear to be of medical importance, having been linked to certain forms of deafness and, possibly, sterility. Here we describe the identification and characterization of a novel FH gene, formin-2 (Fmn2), found in both mice and humans. Expression analysis revealed that this gene was expressed in oocytes and in the developing and mature central nervous system. Functional analysis of Fmn2, via targeted deletion of the gene in mice, demonstrated that Fmn2 is required for normal fertility in female mice. Deletion of the gene leads to recurrent miscarriage. Further analysis revealed that Fmn2 functions to correctly position Metaphase I chromatin at the cortex of the mouse oocyte, a process required for the first asymetrical cell division in meiosis. The extensive similarity in sequence and expression pattern between mouse and human Fmn2, combined with the functional conservation of other FH family members, suggests Fmn-2 plays a similar role in mice and humans. Studying human Fmn2 may, therefore, lead to novel genetic diagnostics for infertility and recurrent miscarriage.