The investigators are interested in understanding specific genetic pathways that are essential for germ cell development. They discovered a previously unknown gene, Hormad1, which encodes a protein with HORMA domain. HORMA is a specialized domain encountered in proteins functioning in meiotic and mitotic spindle checkpoints, chromosome synapsis, and DNA repair. The HORMA domain proteins critical in meiosis were described in yeast, nematodes, and plants, and include Hop1p, Red1p, Him-3, and Asy1. Meiosis specific HORMA domain proteins are critical in synapsis, segregation, and recombination of chromosomes. There are no known meiosis specific HORMA domain proteins in mammals, and no known mammalian homologues to Hop1p, Red1p, Him-3, or Asy1. The investigators hypothesize that Hormad1 encodes a meiosis specific HORMA domain protein in mammals and that it plays critical functions in mammalian germ cell development and meiosis. Their preliminary results suggest that Hormad1 is preferentially expressed in germ cells, and that Hormad1 deficient mice are infertile and hypogonadal. They propose to develop antibodies against HORMAD1 to study its expression, and then determine the cellular as well as meiotic chromosome localization. In addition, they will use the newly created Hormad1 knock-out mouse to delineate the onset of gonadal pathology that leads to male and female infertility. These studies will be important to begin understanding the function of the highly conserved HORMAD1 protein in germ cell development and meiosis I. PROJECT
The investigators identified a novel gene, Hormad1, which encodes a protein likely to be important in mammalian meiosis. Absence of Hormad1 function causes infertility. They will study whether infertility in Hormad1 mice results from abnormal germ cell function.
| Shin, Yong-Hyun; McGuire, Megan M; Rajkovic, Aleksandar (2013) Mouse HORMAD1 is a meiosis i checkpoint protein that modulates DNA double- strand break repair during female meiosis. Biol Reprod 89:29 |
| Shahzad, Mian M K; Shin, Yong-Hyun; Matsuo, Koji et al. (2013) Biological significance of HORMA domain containing protein 1 (HORMAD1) in epithelial ovarian carcinoma. Cancer Lett 330:123-9 |
| Jagarlamudi, Krishna; Rajkovic, Aleksandar (2012) Oogenesis: transcriptional regulators and mouse models. Mol Cell Endocrinol 356:31-9 |
| Shin, Yong-Hyun; Choi, Youngsok; Erdin, Serpil Uckac et al. (2010) Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis. PLoS Genet 6:e1001190 |
