Normal Reproductive and Macrophage Function inPemHomeobox Gene-Deficient Mice

Abstract

Interaction between germ cells and the supporting somatic cells guides many of the differentiative processes of gametogenesis. The expression pattern of the Pem homeobox gene suggests that it may mediate specific 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 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 in Pem have normal fecundity, with no detectable alteration in extraembryonic testicular 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 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 require Pem. No differences were observed between Pem-knockout mice in 129, C57BL6/J, or mixed genetic backgrounds. Together, these data show that Pem is dispensable for embryonic and postnatal development, gonadal function, and Kupffer cell activation, perhaps due to compensatory expression of a similar homeobox gene.

Dynamic expression pattern and subcellular localization of the Rhox10 homeobox transcription factor during early germ cell development

“…By analogy, many other developmentally regulated genes, including Rhox5, have been shown to be expressed in germ cells in one context and somatic cells in another context, i.e. in a different tissue or developmental stage (Eddy & O'Brien 1998, Pitman et al 1998. The region-specific expression pattern of RHOX10 in epididymis (Fig.…”

GATA Factors and Androgen Receptor Collaborate To Transcriptionally Activate theRhox5Homeobox Gene in Sertoli Cells

“…Histological and immunohistochemical analyses were performed as described previously (50). Sections were incubated with rabbit anti-AR polyclonal antiserum (Upstate, Charlottesville, VA) and rabbit anti-GATA2 antibody polyclonal antiserum (Santa Cruz Biotechnology, Inc., Santa Cruz, CA) at 1:500 and 1:2,000 (vol/vol) dilutions, respectively.…”

The Rhox genes

“…Rhox5 is initially expressed in the unfertilized mouse oocyte, remains expressed at low levels in the blastocyst, and later is mainly confined in its expression to male and female primordial germ cells (PGCs) and extra-embryonic tissues, where it is expressed at very high levels (Wilkinson et al 1990, Sasaki et al 1991, Lin et al 1994, Pitman et al 1998, Hamatani et al 2004, Chazaud et al 2006, Daggag et al 2008. After birth, its expression is primarily restricted to specific somatic cells in the reproductive tract: i) Sertoli cells in the testes, ii) principal cells in the epididymis, and iii) granulosa cells in the ovary (Wilkinson et al 1990, Lin et al 1994, Maiti et al 1996a, Pitman et al 1998, Rao et al 2002b. The expression of Rhox5 in Sertoli cells is of interest given that these cells provide a structural framework for spermatogenesis and direct several androgen-dependent steps of spermatogenesis.…”