Lack of acrosome formation in mice lacking a Golgi protein, GOPC

Abstract The acrosomeis a unique organelle that plays an important role at the site of sperm– zona pellucidabinding during the fertilization process, and is lost in globozoospermia, an inherited infertility syndrome in humans. Although the acrosomeis known to be derived from the Golgi apparatus, molecular mechanisms underlying acrosomeformation are largely unknown. Here we show that Golgi-associated PDZ- and coiled-coilmotif-containing protein (GOPC), a recently identified Golgi-associated protein, is predominantly localized at the trans-Golgi region in round spermatids, and male mice in which GOPC has been disrupted are infertile with globozoospermia. The primary defect was the fragmentation of acrosomesin early round spermatids, and abnormal vesicles that failed to fuse to developing acrosomeswere apparent. In later stages, nuclear malformation and an abnormal arrangement of mitochondria, which are also characteristic features of human globozoospermia, were observed. Interestingly, intracytoplasmic sperm injection(ICSI) of such malformed sperm into oocytes resulted in cleavage into blastocysts only when injected oocytes were activated. Thus, GOPC provides important clues to understanding the mechanisms underlying spermatogenesis, and the GOPC-deficient mouse may be a unique and valuable model for human globozoospermia.