HORMAD1 Is Essential for Male and Female Meiosis Figure 10. HORMAD1 is expressed in embryonic but not post-natal oocytes. (A–C) HORMAD1 protein was detected by immunofluorescence in the embryonic ovary at E14.5 (A), E18.5 (B), but not in the newborn ovary (C). (D–F) Oocytes in Hormad12/2 ovary (2/2) were stained with antibodies against the germ cell–specific transcriptional regulator SOHLH1 at E14.5 (D), E18.5 (E), and newborn ovary (F). DNA was stained with DAPI (Blue). Scale bars: 20 mm. doi:10.1371/journal.pgen.1001190.g010 (n = 50). These results indicate importance of Hormad1 in proper spindle formation and segregation. Discussion We discovered Hormad1 (Nohma), using in silico screen to identify germ cell–specific transcripts critical for gonadal development [16]. We showed that Hormad1 expression was confined to germ cells, and that Hormad1 transcripts were mostly concentrated in the pachytene spermatocytes and early oocytes. Here we show that Hormad1 is essential for both male and female fertility in the mouse. HORMA domain-containing proteins interact with chromatin, particularly chromatin associated with DNA adducts, and are critical mitotic spindle checkpoint proteins [5]. HORMA domain-containing proteins are critical regulatory proteins for mitosis as exemplified by MAD2 protein, and meiosis as exemplified by Hop1p [8], and Red1p [9] in yeast, Him-3 [10] in nematodes, and Asy1 [11] in plants. The 205-aa HORMA domain in the mouse HORMAD1, shares highest similarity to the Saccharomyces cerevisiae Hop1 protein (28% amino acid similarity). Yeast Hop1 mutants have defects in chromosome condensation, synapsis and recombination [4,8], and Hop1p binds DSBs during meiotic prophase and appears to play an important role in interhomologue recombination. We previously hypothesized, based on homology to Hop1 in yeast, that Hormad1 Figure 11. Histological analysis of wild-type and Hormad1–/– ovaries. (A–H) PAS staining of wild-type (+/+) and Hormad12/2 (2/2) ovaries does not show gross histological differences. Wild-type and Hormad12/2 ovaries are shown at different post-natal ages that show the full range of ovarian follicles: primordial follicles (PF), primary follicles (PrF), secondary follicles (SF), antral follicles (AF) and corpus luteum (CL). Scale bars: 50 mm. doi:10.1371/journal.pgen.1001190.g011 PLoS Genetics | www.plosgenetics.org 12 November 2010 | Volume 6 | Issue 11 | e1001190