Species: mouse
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Conserved role of nanos proteins in germ cell development. Tsuda M et al. (2003) In Drosophila, maternally supplied Nanos functions in the migration of primordial germ cells (PGCs) into the gonad; in mice, zygotic genes are involved instead. We report the cloning and the functional analyses of nanos2 and nanos3 in mice. These genes are differentially expressed in mouse PGCs. nanos2 is predominantly expressed in male germ cells, and the elimination of this gene results in a complete loss of spermatogonia. However, nanos3 is found in migrating PGCs, and the elimination of this factor results in the complete loss of germ cells in both sexes. Hence, although mice and flies differ in their mechanisms for germ cell specification, there seems to be conserved function for nanos proteins among invertebrates and vertebrates.//////////////////Tsuda M,et al report the cloning and the functional analyses of nanos2 and nanos3 in mice. In the nanos3-null mice, the size of the ovaries and testes were both greatly reduced (the weight of the testes was reduced to about 30% of that of the wild type, which was similar to that observed in nanos2-null mice) (Fig. 2, A and D). No germ cells were observed in sections (Fig. 2, B, C, E, and F). Germ cells were absent even in the E15.5 ovaries and testes (Fig. 2, G and J). Additionally, only a few germ cells were detected in the E12.5 genital ridge (Fig. 2, H, I, K, and L).

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: A NANOS3 mutation linked to protein degradation causes premature ovarian insufficiency. Wu X et al. (2014) Primary ovarian insufficiency (POI), or premature ovarian failure, is defined as the cessation of ovarian function before the age of 40. An insufficient ovarian follicle pool derived from primordial germ cells (PGCs) is an important cause of POI. Although the Nanos gene family is known to be required for PGC development and maintenance in diverse model organisms, the relevance of this information to human biology is not yet clear. In this study, we screened the coding regions of the NANOS1, NANOS2 and NANOS3 genes in 100 Chinese POI patients and identified four variants in the coding regions of these three genes, including one synonymous variant in NANOS3, one missense variant in each of NANOS1 and NANOS2 and one potentially relevant mutation (c.457C>T; p.Arg153Trp, heterozygous) in NANOS3. We demonstrated that the p.Arg153Trp substitution decreases the stability of NANOS3, potentially resulting in a hypomorph. Furthermore, an investigation of the relationship between the number of PGCs and the dosage of NANOS3 in mouse models showed that the population of PGCs is controlled by the level of NANOS3 protein. Taken together, our results provide new insight into the properties of the NANOS3 protein and establish that NANOS3 mutation is one possible cause of POI. //////////////////

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Homozygous inactivating mutation in NANOS3 in two sisters with primary ovarian insufficiency. Santos MG et al. (2015) Despite the increasing understanding of female reproduction, the molecular diagnosis of primary ovarian insufficiency (POI) is seldom obtained. The RNA-binding protein NANOS3 poses as an interesting candidate gene for POI since members of the Nanos family have an evolutionarily conserved function in germ cell development and maintenance by repressing apoptosis. We performed mutational analysis of NANOS3 in a cohort of 85 Brazilian women with familial or isolated POI, presenting with primary or secondary amenorrhea, and in ethnically-matched control women. A homozygous p.Glu120Lys mutation in NANOS3 was identified in two sisters with primary amenorrhea. The substituted amino acid is located within the second C2HC motif in the conserved zinc finger domain of NANOS3 and in silico molecular modelling suggests destabilization of protein-RNA interaction. In vitro analyses of apoptosis through flow cytometry and confocal microscopy show that NANOS3 capacity to prevent apoptosis was impaired by this mutation. The identification of an inactivating missense mutation in NANOS3 suggests a mechanism for POI involving increased primordial germ cells (PGCs) apoptosis during embryonic cell migration and highlights the importance of NANOS proteins in human ovarian biology. //////////////////

Species: None
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: nanos3 maintains germline stem cells and expression of the conserved germline stem cell gene nanos2 in the zebrafish ovary. Beer RL et al. (2013) Female zebrafish have a prolific reproductive capacity, suggesting that a germline stem cell (GSC) population drives oocyte production. However, a zebrafish female GSC population has yet to be identified. Adult stem cells are defined by their ability to both self-renew and differentiate, and by their localization to a stem cell niche. We show here that mitotic and early meiotic germ cells are present in the adult ovary and that the zebrafish homolog of the conserved vertebrate GSC marker, nanos2, is expressed in a subset of pre-meiotic oogonia in the adult gonad. We propose that these nanos2(+) cells are GSCs. Importantly, we find that mitotic, nanos2(+), and early meiotic germ cells localize to the germinal zone, thus identifying this region as the probable ovarian GSC niche in zebrafish. nanos3, which encodes a conserved RNA-binding protein, is known to be required for the continued production of oocytes in the zebrafish. Although mammalian homologs of nanos3 are expressed in early spermatogonia, no study has defined the role of nanos3 in the regulation of vertebrate GSCs. Here we demonstrate that nanos3 function is required for the maintenance of GSCs, but not for their specification, and propose that nanos2 and nanos3 are partially redundant in this role.//////////////////

Species: mouse
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Conserved role of nanos proteins in germ cell development. Tsuda M et al. (2003) In Drosophila, maternally supplied Nanos functions in the migration of primordial germ cells (PGCs) into the gonad; in mice, zygotic genes are involved instead. We report the cloning and the functional analyses of nanos2 and nanos3 in mice. These genes are differentially expressed in mouse PGCs. nanos2 is predominantly expressed in male germ cells, and the elimination of this gene results in a complete loss of spermatogonia. However, nanos3 is found in migrating PGCs, and the elimination of this factor results in the complete loss of germ cells in both sexes. Hence, although mice and flies differ in their mechanisms for germ cell specification, there seems to be conserved function for nanos proteins among invertebrates and vertebrates.//////////////////