Background: Preterm birth is the leading cause of all infant mortality. In 2004, 12.5% of all births were preterm. In order to understand preterm labor, we must first understand normal labor. Since many of the myometrial changes that occur during pregnancy are similar in mice and humans and mouse gestation is short, we have studied the uterine genes that change in the mouse during pregnancy. Here, we used microarray analysis to identify uterine genes in the gravid mouse that are differentially regulated in the cyclooxygenase-1 knockout mouse model of delayed parturition.
Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxygenase-1 knockout mouse.
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Activity-dependent regulation of inhibitory synapse development by Npas4.
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Knockout of G protein β5 impairs brain development and causes multiple neurologic abnormalities in mice.
Specimen part
View SamplesThis data series was used for two separate studies. The initial study was aimed to idenify expression changes brought about by the Cecr2Gt45Bic mutation during neural closure. The study included two different strains, BALB/cCrl in which Cecr2GT45Bic shows a neural tube defect phenotype and FVB/N in which Cecr2Gt45Bic does not manifest neural closure defects. The second was to idenify strain specific expression differences present during neural closure of the mouse embryo between BALB/cCrl and FVB/N in order to identify candidate modifiers of the Cecr2Gt45Bic neural tube defect. Relevant abstracts are included below.
Strain-specific modifier genes of Cecr2-associated exencephaly in mice: genetic analysis and identification of differentially expressed candidate genes.
Sex, Specimen part
View SamplesThymic stromal lymphopoietin (TSLP) is a type I cytokine that plays a central role in induction of allergic inflammatory responses. Its principal targets have been reported to be dendritic cells and / or CD4 T cells; epithelial cells are a principal source. We report here the development of a reporter mouse (TSLP-ZsG) in which a ZsGreen (ZsG)-encoding construct has been inserted by recombineering into a bacterial artificial chromosome (BAC) immediately at the translation initiating ATG of TSLP. The expression of ZsG by mice transgenic for the recombinant BAC appears to be a faithful surrogate for TSLP expression, particularly in keratinocytes and medullary thymic epithelials cells (mTECs). A comparison of gene expression in ZsG expressing and ZsG negative mTECs and cortical thymic epithelial cells, which are all ZsG negative, revealed that all three populations can be distinguished from one another. In particular ZsG (and TSLP) expressing mTECs and ZsG- mTECs are separable populations based on gene expression profiling. Little or no expression of ZsG is observed in bone marrow-derived mast cells or basophils or in CD45+ cells infiltrating TSLP/ZsG-expressing skin. Using the TSLP-ZsG reporter mouse, we show that TNFa and IL-4/IL-13 are potent inducers of TSLP expression by keratinocytes and that local activation of Th2 and Th1 cells induces keratinocyte TSLP expression. We suggest that the capacity of TSLP to both induce Th2 differentiation and to be induced by activated Th2 cells raises the possibility that TSLP may be involved in a positive feedback loop to enhance allergic inflammatory conditions.
TSLP expression: analysis with a ZsGreen TSLP reporter mouse.
Specimen part, Treatment
View SamplesWe sequenced liver mRNA isolated from biliatresone-treated zebrafish larvae and DMSO-treated controls in order to elucidate the molecular pathways induced by biliatresone, a biliary toxin that is responsible for outbreaks of biliary atresia in Australian liverstock. Overall design: Liver mRNA profiles of biliatresone-treated zebrafish larvae and DMSO-treated controls were generated by deep sequencing, in duplicates.
Glutathione antioxidant pathway activity and reserve determine toxicity and specificity of the biliary toxin biliatresone in zebrafish.
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View SamplesGinkgo biloba leaf extract (GBE) has been used for centuries in traditional Chinese medicine and today is used as an herbal supplement for various indications such as improving neural function, anti-oxidant and anti-cancer effects. As part of the herbal supplement industry, these compounds are largely unregulated, and may be consumed in large concentrations over extended periods of time. This is of particular concern, because the long-term effects in terms of toxicity and carcinogenicity data is lacking for many herbal products, including GBE. The 2-year B6C3F1 mouse carcinogenicity bioassay indicated a marked dose-related increase in hepatocellular carcinoma (HCC) development associated with exposure to GBE. We have shown that the mechanism of this increase in tumorigenesis is related to a marked increase in the incidence of -catenin mutation, and report a novel mechanism of constitutive -catenin activation through post-translational modification leading to constitutive Wnt signaling and unregulated growth signaling and oncogenesis. Furthermore, using global gene expression profiling, we show that GBE-induced HCC exhibit overrepresentation of gene categories associated with human cancer and HCC signaling including upregulation of relevant oncogenes and suppression of critical tumor suppressor genes, as well as chronic oxidative stress, a known inducer of calpain-mediated degradation and promoter of hepatocarcinogenesis in humans. These data provide a molecular mechanism to GBE-induced HCC in B6C3F1 mice that is relevant to human cancer, and provides relevant molecular data that will provide the groundwork for further risk assessment of unregulated compounds, including herbal supplements.
Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways.
Specimen part
View SamplesMice lacking the function of the PcG protein CBX2 (also known as M33) show defects in gonadal, adrenal, and splenic development. In particular, XY knockout mice develop ovaries but not testes, and the gonads are hypoplastic in both sexes.
Cbx2, a polycomb group gene, is required for Sry gene expression in mice.
Specimen part
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Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
Treatment
View SamplesWe examined transgenic (TG) mice expressing human APP695 bearing the double Swedish (671KM>NL) and Indiana (717V>F) amyloid precursor protein (APP) mutations. Lentiviral vectors constitutively expressing BDNF-GFP under control of the CMV/-actin hybrid promoter or GFP alone were injected into the entorhinal cortices of TG mice bilaterally at age 6 months, a time point by which neuropathological degeneration and cell loss are established. Age-matched wild-type littermates underwent sham surgery or injection of lentivirus expressing GFP into the entorhinal cortices bilaterally.
Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
Treatment
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