Project description:This SuperSeries is composed of the following subset Series: GSE29192: Implication of Nos2 inactivation on the transcriptome of developing cerebellum and Ptch1+/- medulloblastomas (mRNA) GSE29199: Implication of Nos2 inactivation on genomic changes in Ptch1+/- medulloblastomas (array-CGH) Refer to individual Series
Project description:The Ptch1+/- strain constitues an established mouse model for the Shh-driven type of medulloblastoma. Combined Ptch1+/- Nos2-/- mice show a two-fold increased incidence for this tumor. Here, the impact of Nos2 inactivation on medulloblastoma development was investigated by gene expression profiling of tumor samples as well as healthy cerebellum at different ages and genotypes. Medulloblastoma samples from three Ptch1+/- and six combined Ptch1+/- Nos2-/- mice were analyzed. Healthy cerebellum taken from mice at postnatal day nine, six weeks after birth, and about 1 year of age were analyzed for wildtype animals and the genotypes Ptch1+/-, Ptch1+/- Nos2-/-, and Nos2-/-. The cerebellar developmental stages at six weeks and one year were measured in three biological replicates, while samples taken at postnatal day six consisted of pooled individual specimen. These were measured in three replicates being amplified and labelled in separate reactions. All samples were subjected to two-color hybridizations against Universal Reference RNA (Stratagene) with color-switch experiments yielding two technical replicates, respectively.
Project description:The Ptch1+/- strain constitues an established mouse model for the Shh-driven type of medulloblastoma. Combined Ptch1+/- Nos2-/- mice show a two-fold increased incidence for this tumor. Here, the impact of Nos2 inactivation on medulloblastoma development was investigated by gene expression profiling of tumor samples as well as healthy cerebellum at different ages and genotypes.
Project description:The Ptch1+/- strain constitues an established mouse model for the Shh-driven type of medulloblastoma. Combined Ptch1+/- Nos2-/- mice show a two-fold increased incidence for this tumor. Here, the impact of Nos2 inactivation on copy number alterations during medulloblastoma development was investigated by array-based comparative genomic hybridization (arrayCGH) of tumor samples from both genotypes. Medulloblastoma samples from five Ptch1+/- and seven compound Ptch1+/- Nos2-/- mice were analyzed. Cy5-labeled tumor DNA was combined with corresponding Cy3-labeled reference healthy wildtype genomic DNA to receive either sex-matched sample pairs or pairs of different gender for internal negative or positive control.
Project description:The Ptch1+/- strain constitues an established mouse model for the Shh-driven type of medulloblastoma. Combined Ptch1+/- Nos2-/- mice show a two-fold increased incidence for this tumor. Here, the impact of Nos2 inactivation on copy number alterations during medulloblastoma development was investigated by array-based comparative genomic hybridization (arrayCGH) of tumor samples from both genotypes.
Project description:To investigate Pten function in neonatal developing brain, we conditionally inactivated Pten in neural stem/progenitor cells at birth using a Nestin-CreER transgenic driver. Pten inactivation created a novel perivascular proliferative niche in the cerebellum that did not progress to malignancy during the lifespan of the mouse. Co-deletion of Pten and Trp53 synergized to cause fully penetrant medulloblastoma originating from a perivascular niche. The Pten and Trp53 double knock-out medulloblastomas showed an extensive and abnormal blood vessel network and advanced neuronal differentiation of tumor cells compared to medulloblastomas arising in Nestin-creER;Trp53fl/fl mice, suggesting that Pten loss promoted angiogenesis and neuronal differentiation in medulloblastoma. EdU pulse-chase experiments demonstrated a lineage hierarchy of the double knock-out medulloblastomas consistent with a perivascular cancer stem cell population. The Pten and Trp53 double knock-out medulloblastomas showed somatic loss of chromosomes 7, 13 and 16, and inactivating mutations in the tumor suppressor gene Ptch1. Gene expression profiles showed that this model recapitulated the subgroup of human medulloblastomas with de-regulated SHH signaling.
Project description:This SuperSeries is composed of the following subset Series: GSE19360: Integrated array-CGH and expression microarray analyses on medulloblastomas in heterozygous Ptch1 mice, expression GSE19381: Integrated array-CGH and expression microarray analyses on medulloblastomas in heterozygous Ptch1 mice, aCGH 1 GSE19382: Integrated array-CGH and expression microarray analyses on medulloblastomas in heterozygous Ptch1 mice, aCGH 2 Refer to individual Series
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.