University of Hawaiʻi Researchers Develop New Mouse Models to Study Male Fertility Gene ZFY

Researchers at the University of Hawaiʻi at Mānoa have developed novel mouse models designed to investigate the Y chromosome gene ZFY, which is critical for male fertility. Published in BMC Genomics, this study aims to provide insights into male infertility by enabling detailed tracking of ZFY proteins and identifying genes it regulates, potentially informing future diagnosis and treatment strategies.

Research Overview

The study was led by Professor Monika Ward from the John A. Burns School of Medicine and the Yanagimachi Institute for Biogenesis Research at the University of Hawaiʻi at Mānoa. The research focuses on the ZFY gene, a Y chromosome gene crucial for male fertility.

Previous work by Professor Ward’s team indicated that male mice lacking both copies of the Zfy gene (the mouse versions known as Zfy1 and Zfy2) were completely infertile. These earlier studies also showed that such mice exhibited widespread disruption of genes involved in sperm development and cell survival. ZFY is understood to function as a transcription factor, meaning it plays a role in switching other genes on and off.

Development of New Mouse Models

To further investigate the ZFY gene, the research team utilized CRISPR-Cas9 genome editing technology. This technique was employed to add molecular "tags" to the Zfy1 and Zfy2 genes in the mouse models. These tags facilitate the detection, isolation, and detailed study of the Zfy proteins produced by these genes.

Using these newly developed tagged mouse models, researchers were able to identify, for the first time, which specific male germ cells produce Zfy1 and Zfy2 proteins and at what levels within those cells.

Implications for Male Infertility Research

The new mouse models are designed to assist in identifying which specific genes ZFY regulates, building on its known role as a transcription factor. This information is considered relevant for advancing the understanding of spermatogenesis—the process of sperm development—and for guiding the diagnosis and treatment of male infertility.

Professor Ward stated that the new mice provide a necessary tool for continuing investigations into how Zfy controls spermatogenesis.