Mammalian females are born with a finite number of non-renewing primordial follicles, the majority of which remain in a quiescent state for many years. Due to their non-renewing nature, these resting oocytes are particularly vulnerable to xenobiotic insult, resulting in premature ovarian senescence and the formation of dysfunctional oocytes. In this study we characterised the mechanisms of ovotoxicity for three ovotoxic agents, 4-Vinylcyclohexene Diepoxide (VCD), Methoxychlor (MXC), and Menadione (MEN), all of which target immature follicles. Neonatal mouse ovaries (PND3-4) were cultured in the presence of 4-Vinylcyclohexene Diepoxide (50uM), Methoxychlor (50uM), and Menadione (5uM) for 96 hours to observe their effects on the ovarian transcriptome. This was done in the hopes of gaining a better understanding of the mechanisms underpinning xenobiotic induced pre-antral ovotoxicity.
Adding insult to injury: effects of xenobiotic-induced preantral ovotoxicity on ovarian development and oocyte fusibility.
Specimen part
View SamplesIdentification of imprinted genes expressed in adult CD3+ splenocytes
Hematopoietic reconstitution with androgenetic and gynogenetic stem cells.
Sex, Age, Specimen part
View SamplesIn euakryotes, mRNAs must be exported from the nucleus to the cytsoplasm. NXF2 is highly expressed in the mouse male germ cells. We are interested in its function in spermatogenesis, espically in the nuclear RNA export in the testis. To this end, we made Nxf2 mutant mice by gene targeting. In an attempt to identify the mRNA substrates of NXF2, we perform the microarray experiments on testes.
Inactivation of Nxf2 causes defects in male meiosis and age-dependent depletion of spermatogonia.
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View SamplesThe two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs with small molecule inhibitors of Gsk-3 phenocopies the DNA hypomethylation of imprinted loci observed in Gsk-3 null ESCs. We provide evidence that DNA hypomethylation in Gsk-3 null ESCs is due to a reduction in the levels of the de novo DNA methyltransferase, Dnmt3a2.
Phosphatidylinositol 3-kinase (PI3K) signaling via glycogen synthase kinase-3 (Gsk-3) regulates DNA methylation of imprinted loci.
Specimen part
View SamplesAs a critical cellular stress sensor, p53 mediates a variety of defensive processes including cell-cycle arrest, apoptosis, and senescence to prevent propagation of hyperproliferative cells or cells with a damaged genome, hence the formation of neoplasia. Transactivation of downstream genes plays an important while sometimes controversial role in regulating these cellular processes. To evaluate the dependence on transcriptional activation in p53s activities, we generated genetically-modified mouse lines carrying mutations in the transactivation domains (TADs) of p53. These transactivatio-deficient mutants serve as unique reagents to probe the dependence on robust transactivation in p53-mediated cellular functions, as well as the underneath mechanisms. To identify genes differentially regulated by these p53 mutants, we performed gene expression profiling analysis on mouse embryonic fibroblast cells (MEFs) from these mice in the context of oncogenic Ras-induced premature cellular senescence.
Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression.
Specimen part
View SamplesGene expression profiling of zebrafish early eye development on 3 to 5 days post fertilization (dpf)
Integrating multiple genome annotation databases improves the interpretation of microarray gene expression data.
Specimen part
View SamplesMedulloblastoma (MB) is the most common malignant brain tumor in children. Patients whose tumors exhibit overexpression or amplification of the MYC oncogene (c-MYC) usually have an extremely poor prognosis, but there are no animal models of this subtype of the disease. Here we show that cerebellar stem cells expressing Myc and mutant Trp53 (p53) generate aggressive tumors following orthotopic transplantation. These tumors consist of large, pleiomorphic cells and resemble human MYC-driven MB at a molecular level. Notably, antagonists of PI3K/mTOR signaling, but not Hedgehog signaling, inhibit growth of tumor cells. These findings suggest that cerebellar stem cells can give rise to MYC-driven MB, and identify a novel model that can be used to test therapies for this devastating disease.
An animal model of MYC-driven medulloblastoma.
Specimen part
View SamplesAffymetrix Human Gene 1.1 ST Array profiling of 285 primary medulloblastoma samples.
Subgroup-specific structural variation across 1,000 medulloblastoma genomes.
Sex, Age
View Samples