Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA111517 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Expression profiling of thymic lymphomas derived from HIF1a+/+, p53R270H/R270H; HIF1a+/-, p53R270H/R270H; and HIF1aKI/+, p53R270H/R270H mice. HIF1a and HIF2a share a high degree of sequence homology, but recent work has shown that the two a subunits can have contrasting and tissue-specific effects on tumor growth. To directly compare the role of each HIFa subunit in spontaneous tumorigenesis, we bred a mouse model of expanded HIF2a expression and Hif1a+/- mice to homozygotes for the R270H mutation in p53. Heterozygosity for Hif1a significantly reduced the incidence of thymic lymphomas observed in this model. Moreover, reduced Hif1a levels correlated with decreased stabilization of activated Notch1 and expression of the Notch target genes, Dtx1 and Nrarp. Keywords: genetic modification, disease state analysis Thymic lymphoma tissue was preserved at the time mice were sacrificed. 4-5 samples from each of 3 genotypes (HIF1a+/-, p53R270H/R270H, HIF1aKI/+; p53R270H/R270H; and HIF1a+/+, p53R270H/R270H) were then used for microarray analysis to identify differences in gene expression that could account for changes in tumor onset and incidence.
2009-01-12 | E-GEOD-14336 | biostudies-arrayexpress
Project description:Expression profiling of thymic lymphomas derived from HIF1a+/+, p53R270H/R270H; HIF1a+/-, p53R270H/R270H; and HIF1aKI/+, p53R270H/R270H mice. HIF1a and HIF2a share a high degree of sequence homology, but recent work has shown that the two a subunits can have contrasting and tissue-specific effects on tumor growth. To directly compare the role of each HIFa subunit in spontaneous tumorigenesis, we bred a mouse model of expanded HIF2a expression and Hif1a+/- mice to homozygotes for the R270H mutation in p53. Heterozygosity for Hif1a significantly reduced the incidence of thymic lymphomas observed in this model. Moreover, reduced Hif1a levels correlated with decreased stabilization of activated Notch1 and expression of the Notch target genes, Dtx1 and Nrarp. Keywords: genetic modification, disease state analysis
2009-01-12 | GSE14336 | GEO
Project description:Apc(D716) mutant mice develop benign intestinal adenoma, while Apc(D716) and p53 R270H compound mutant mice develop invasive adenocarcinoma in the intestine. We examined expression profile of tumor-derived organoids using Apc(D716), Apc(D716) p53 Null, Apc(D716) p53 R270H mutant mice by RNA sequencing, and identified mutant p53-induced gene set.
2017-02-01 | GSE81441 | GEO
Project description:RNA sequencing of Mus musculus thymic lymphomas
2019-06-06 | GSE85894 | GEO
Project description:RNA sequencing of Mus musculus thymic lymphomas
2020-12-30 | GSE121739 | GEO
Project description:Our group previously demonstrated that the Trp53 R270H mutation can drive prostate cancer (CaP) initiation in a genetically engineered mouse model (FVB.129S4(Trp53tm3Tyj/wt);FVB.129S(Nkx3-1tm3(cre)Mmswt)). The objective of the current study was to identify molecules that may facilitate Trp53 R270H-mediated prostate carcinogenesis. Mice that harbor a Trp53 R270H germline mutation (B6.129S4-Trp53tm3.1Tyj/J) were used for the current study. Wildtype (Trp53WT/WT), heterozygous (Trp53R270H/WT), and homozygous mice (Trp53R270H/R270H) were exposed to 5 Gy radiation to activate and stabilize p53 and thereby enhance our ability to identify differences in transcriptional activity between the 3 groups of mice. Mouse prostates were harvested 6 hours post-irradiation and either processed for histological/immunohistochemistry (IHC) analysis or snap-frozen for RNA extraction and transcriptome profiling with RNA-Sequencing (RNA-Seq) analysis. IHC was used to assess cell proliferation (Ki67) and apoptosis (activated caspase 3). PIN lesions were observed in heterozygous and homozygous mice as early as 3 months, thereby validating our prior finding that the Trp53 R270H mutation can drive CaP initiation. RNA-Seq analysis identified 1,378 differentially expressed genes, including multiple wildtype p53 target genes (E.g. Cdkn1a, Bax, Bcl2, Kras, Mdm2), p53 gain-of-function (GOF) genes (Mgmt, Id4), and CaP-related genes (Cav-1, Raf1, Kras). Our combined data validate a role for the Trp53 R270H mutation in CaP initiation, and identify molecules that may contribute to Trp53 R270H-mediated prostate carcinogenesis.
2022-03-02 | GSE130440 | GEO
Project description:The specific roles of mutant p53’s dominant-negative (DN) or gain-of-function (GOF) properties in regulating acute response and long-term tumorigenesis is unclear. Using “knock-in” mouse strains expressing varying R246S mutant levels, we show that DN effect on transactivation is universally observed after acute p53 activation whereas the effect on cellular outcome is cell-type specific. Reducing mutant p53 levels abrogated the DN effect. Mutant p53’s DN effect protected against radiation-induced death, but did not accentuate tumorigenesis. Furthermore, the R246S mutant did not promote tumorigenesis compared to p53-/- mice in various models, even in the absence of MDM2, unlike the R172H mutant. Together, these data demonstrate that mutant p53’s DN property only affects acute responses, whereas GOF is not universal, being mutation-type specific.
2012-12-31 | GSE40416 | GEO
Project description:The specific roles of mutant p53’s dominant-negative (DN) or gain-of-function (GOF) properties in regulating acute response and long-term tumorigenesis is unclear. Using “knock-in” mouse strains expressing varying R246S mutant levels, we show that DN effect on transactivation is universally observed after acute p53 activation whereas the effect on cellular outcome is cell-type specific. Reducing mutant p53 levels abrogated the DN effect. Mutant p53’s DN effect protected against radiation-induced death, but did not accentuate tumorigenesis. Furthermore, the R246S mutant did not promote tumorigenesis compared to p53-/- mice in various models, even in the absence of MDM2, unlike the R172H mutant. Together, these data demonstrate that mutant p53’s DN property only affects acute responses, whereas GOF is not universal, being mutation-type specific.
2012-12-31 | GSE40415 | GEO
Project description:The specific roles of mutant p53’s dominant-negative (DN) or gain-of-function (GOF) properties in regulating acute response and long-term tumorigenesis is unclear. Using “knock-in” mouse strains expressing varying R246S mutant levels, we show that DN effect on transactivation is universally observed after acute p53 activation whereas the effect on cellular outcome is cell-type specific. Reducing mutant p53 levels abrogated the DN effect. Mutant p53’s DN effect protected against radiation-induced death, but did not accentuate tumorigenesis. Furthermore, the R246S mutant did not promote tumorigenesis compared to p53-/- mice in various models, even in the absence of MDM2, unlike the R172H mutant. Together, these data demonstrate that mutant p53’s DN property only affects acute responses, whereas GOF is not universal, being mutation-type specific.
2012-12-31 | GSE40414 | GEO