Analysis of the molecular mechanism of sperm head formation using gene-manipulated animals

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SPACA1 is a membrane protein that localizes in the equatorial segment of spermatozoa in mammals and is reported to function in sperm. egg fusion. We produced a Spaca1 gene-disrupted mouse line and found that the male mice were infertile. However, the cause of this sterility turned out to be abnormal shaping of the sperm head reminiscent of globozoospermia in humans. Disruption of Spaca1 led to disappearance of the nuclear plate, a dense lining structure of the nuclear envelope facing the inner acrosomal membrane. This coincided with the failure of acrosomal expansion during spermiogenesis and resulted in the degeneration and disappearance of the acrosome in mature spermatozoa. Thus, one of the mechanisms leading to globozoospermia has been clarified.