Slc30a4, also known as ZnT4, is a zinc transporter gene. It plays a crucial role in zinc transport, specifically transporting zinc into the trans-Golgi apparatus for lactose synthesis and across the apical cell membrane for efflux from mammary epithelial cells (MECs) into milk. This function is essential for maintaining zinc homeostasis in relevant tissues and is associated with processes like lactation [1,2,3]. Genetic models, such as mouse models, are valuable for studying its functions.

In ZnT4-null ("lethal milk") mice, which have a truncation mutation in SLC30A4, there are significant defects. They have smaller mammary glands, decreased milk volume, and lactation failure by lactation day 2. These mice show fewer, smaller, and collapsed alveoli with swollen, lipid-filled MECs during early lactation. The defects are associated with decreased Akt expression and STAT5 activation, indicating problems in MEC secretion. Also, increased expression of ZnT2, TNF-α, and cleaved e-cadherin along with increased STAT3 activation suggest precocious involution, highlighting the importance of Slc30a4 in normal mammary gland function during lactation [1].

In conclusion, Slc30a4 is vital for normal mammary gland secretion and lactation. The study of ZnT4-null mouse models has revealed its significant role in maintaining proper MEC function and tissue remodeling during early lactation. Understanding Slc30a4's function can provide insights into lactation-related disorders and zinc-related metabolic processes.