CRISPR sheds light on genes essential for sperm production in mice

CRISPR/Cas9 genome editing has been used in mice to investigate two key genes' roles in male fertility and sperm production.

Male mice have two genes on the Y chromosome called Zfy1 and Zfy2 that are essential for sperm production. To understand the role of the proteins encoded by these genes, researchers from the University of Hawaii at Mānoa used CRISPR/Cas9 genome editing to insert tags into these genes, allowing the corresponding proteins to be tracked in the testes, providing insight into their roles in the mechanism of spermatogenesis.

'We have been after the Zfy genes for a long time! We knew how important Zfys are for male fertility for quite a while, but were unable to learn how exactly they work,' said Professor Monika Ward, lead author of the paper published in BMC Genomics.

Using the tagging technique, the group were able to produce three different variants of model mice: those with a Zfy1 tag, those with a Zfy2 tag and those where both versions of the protein were tagged. These mice were otherwise unaltered, ensuring that they remained fertile.

Immunofluorescence was then used to identify the presence of the Zfy proteins throughout the testes of the mice, allowing the team to locate which cells express each of these key proteins, and how strongly they do so.

'The new mice represent a much-needed tool to continue the investigations to determine how Zfy controls spermatogenesis,' added Professor Ward.

Professor Ward's group previously published several studies that used genome editing to explore the role of the Zfy genes and their corresponding proteins in the production of healthy sperm. This has included producing double knockout mice that proved to be completely incapable of producing healthy, functional sperm (see BioNews 1306).

Last year the group won a $2.4 million grant to support their research, including into how the equivalent ZFY gene in humans may impact male reproduction and fertility. They also want to extend their research to other genes that may play key roles in normal spermatogenesis.