Slc39a3, also known as Zip3, is a zinc transporter gene. The SLC39 family members, including Slc39a3, are mainly located on the cell membrane, performing zinc uptake and increasing cytosolic zinc availability [2]. Zinc is essential for many biological processes, and thus, Slc39a3 is crucial for maintaining cellular zinc homeostasis.

In lactating mammary gland, studies using Zip3-null mice showed that Zip3 is expressed in secretory mammary cells but does not play a major role in zinc import from the maternal circulation. Instead, it is mainly localized to the luminal membrane of these cells, and functions in the reuptake of zinc from the alveolar lumen, regulating cellular function. Zip3-null mice also had altered mammary tissue architecture, increased apoptotic cells, and reduced mammary gland weight, suggesting its role in apoptosis regulation [1].

In another study, Zip3-null mice under normal growth conditions showed no obvious phenotypic abnormalities, but when stressed with a zinc-deficient diet during pregnancy or at weaning, there was a subtle increase in sensitivity to abnormal embryo morphogenesis and thymic pre-T cell depletion, indicating an ancillary role in zinc homeostasis [3].

In conclusion, Slc39a3 is an important zinc transporter gene, playing a role in zinc reuptake and cellular retention in lactating mammary gland and having an ancillary function in zinc homeostasis in mice. The use of gene-knockout mouse models has provided insights into its functions in specific biological processes and responses to stress, which may be relevant to understanding related physiological and pathological conditions [1,3].