NORMAL REPRODUCTIVE AND MACROPHAGE FUNCTION IN PEM HOMEOBOX GENE-DEFICIENT MICE

Interaction between germ cells and the supporting somatic cells guides many of the differentiative processes of gametogenesis. The expressio n pattern of the Pem homeobox gene suggests that it may mediate specif ic inductive events in murine reproductive tissues. During gestation, Pem is expressed in migrating and early postmigratory primordial germ cells, as well as in all embryo-derived extraembryonic membranes. Pem expression 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, Pem is produced by testicular Sertoli cells during sta ges VI-VIII of spermatogenesis and transiently by ovarian granulosa ce lls lining periovulatory follicles. Despite this tightly regulated rep roductive expression pattern, mice with a targeted mutation in Pem hav e normal fecundity, with no detectable alteration in extraembryonic te sticular or ovarian development or function, We also show that Pem is expressed throughout embryonic and adult development in a subset of a tissue-specific class of macrophages, Kupffer cells, as well as in a l ocalized fraction of cells in macrophage cell lines, Although the numb er of Pem-positive Kupffer cells increases in mice treated with lipopo lysaccharide, loss of Pem does not detectably interfere with the cells ' ability to induce iNOS expression, demonstrating this Kupffer cell f unction does not require Fern. No differences were observed between Pe m-knockout mice in 129, C57BL6/J, or mixed genetic backgrounds. Togeth er, these data show that Pem is dispensable for embryonic and postnata l development, gonadal function, and Kupffer cell activation, perhaps due. to compensatory expression of a similar homeobox gene. (C) 1998 A cademic Press.