Normal Reproductive and Macrophage Function inPemHomeobox Gene-Deficient Mice

AbstractInteraction between germ cells and the supporting somatic cells guides many of the differentiative processes of gametogenesis. The expression pattern of thePemhomeobox gene suggests that it may mediate specific inductive events in murine reproductive tissues. During gestation,Pemis expressed in migrating and early postmigratory primordial germ cells, as well as in all embryo-derived extraembryonic membranes.Pemexpression ceases in the germline after Embryonic Day 14 in both sexes and then reappears postnatally in the supporting cells of the gonad. In mature mice,Pemis produced by testicular Sertoli cells during stages VI–VIII of spermatogenesis and transiently by ovarian granulosa cells lining periovulatory follicles. Despite this tightly regulated reproductive expression pattern, mice with a targeted mutation inPemhave normal fecundity, with no detectable alteration in extraembryonic testicular or ovarian development or function. We also show thatPemis expressed throughout embryonic and adult development in a subset of a tissue-specific class of macrophages, Kupffer cells, as well as in a localized fraction of cells in macrophage cell lines. Although the number of Pem-positive Kupffer cells increases in mice treated with lipopolysaccharide, loss of Pem does not detectably interfere with the cells' ability to induce iNOS expression, demonstrating this Kupffer cell function does not requirePem.No differences were observed between Pem-knockout mice in 129, C57BL6/J, or mixed genetic backgrounds. Together, these data show thatPemis dispensable for embryonic and postnatal development, gonadal function, and Kupffer cell activation, perhaps due to compensatory expression of a similar homeobox gene