Project description:We used an experimental mouse model to further evaluate whether constitutive p53 deficiency in the germ line may increase the rate of de novo CNV in the offspring. C57Bl6 mice with defined trp53 status (either +/+, +/- or -/-) were crossed with 129SvSL trp53+/+ mice and 129SvSL trp53-/- mice were crossed with C57Bl6 trp53+/+ mice. CNV were analyzed in DNA isolated from whole F1 embryos at 17.5 days and compared with liver DNA from their parents. One out of 36 embryo from trp53+/+ parents was detected to have a potential de novo CNV. No de novo CNV was detected in 84 embryos with a p53 deficient parent. These observations suggest that, in this mouse model, partial or complete deficiency of p53 function in the germ line does not increase the rate of CNV formation in the offspring. Affymetrix Mouse Diversity Genotyping Array was performed at The Jackson Lab
Project description:Many preclinical therapy studies have focused on a small number of well-described mouse allograft or human xenograft models that poorly represent the heterogeneity of human disease. Here we have assembled a panel of mouse mammary cell lines derived from spontaneously-arising mouse mammary tumors or from mammary tumors arising in genetically engineered mouse models. We used the Affymetrix Mouse Diversity Genotyping Array to address DNA copy number variation in the genomes of the cell lines of this panel. The resulting information about regions of amplification and deletion should help inform biological analyses as well as provide a reference for cell line authentication/identification. Affymetrix Mouse Diversity Genotyping arrays were used according to manufacturer's directions to analyze gDNA extracted from 27 mouse mammary cell lines of varying malignancy.
Project description:CD23, the low affinity receptor for IgE, has been proposed to play a critical role in the regulation of IgE production, based on altered IgE levels in CD23-deficient mice and transgenic mouse models, as well as in mouse strains with mutations in the CD23 gene, e.g. 129 substrains. Here, we have investigated a mouse line termed LxT1 that expresses reduced CD23 surface levels on B cells, and its influence on IgE production. Extensive phenotypic analyses showed that CD23 surface expression was reduced in LxT1 compared to the control, without affecting B cell development in general. We linked the CD23low surface level in LxT1 mice to a recessive locus, a 129-derived region spanning 28Mb on chromosome 8, which includes the CD23 gene. Sequence analysis confirmed the five mutations within the CD23 coding region in LxT1 mice, the same as those present in NZB and 129 substrains. However, this CD23low phenotype was not observed in all 129 substrains despite carrying these same CD23 mutations in the coding region. Affymetrix Mouse Diversity Genotyping Array was performed according to the manufacturer's directions on DNA extracted from crossed mice samples. The array can interrogate more than 623,000SNPs, yielding an average SNP density of one marker per 4.3kb. Genetic linkage analysis was performed to exploit the co-segregation of chromosomal regions with the CD23 phenotype to identify the location of causative genes.
Project description:Comparison of Genotyping using pooled DNA samples (Allelotyping) and Individual Genotyping using the Affymetrix Genome-Wide Human SNP Array 6.0 In this study, data from 100 DNA samples individually genotyped with the Affymetrix Genome-Wide Human SNP Array 6.0 were used to estimate the error of the pooling approach by comparing the results with those obtained using the same array type but DNA pools each composed of 50 of the same samples. Newly developed and established methods for signal intensity correction were applied. Furthermore, the relative allele intensity signals (RAS) obtained by allelotyping were compared to the corresponding values derived from individual genotyping. Similarly, differences in RAS values between pools were determined and compared.
Project description:Many preclinical therapy studies have focused on a small number of well-described mouse allograft or human xenograft models that poorly represent the heterogeneity of human disease. Here we have assembled a panel of mouse mammary cell lines derived from spontaneously-arising mouse mammary tumors or from mammary tumors arising in genetically engineered mouse models. We used the Affymetrix Mouse Diversity Genotyping Array to address DNA copy number variation in the genomes of the cell lines of this panel. The resulting information about regions of amplification and deletion should help inform biological analyses as well as provide a reference for cell line authentication/identification.