Project description:We generated Ikkα-KA/KA knock-in mice (KA/KA), in which an ATP binding site of Ikkα Lys 44 was replaced by alanine. The knock-in mice develop severe skin lesions and begin to die after 6 to 10 months. We also found lung SCCs in some of the mice. To study lung SCC development, we stabilize the skin condition by crossing KA/KA with Lori.Ikkα transgenic mice to generate KA/KA-Lori.Ikkα mice, which 100% spontaneously developed lethal lung SCC at 4 to 6 months of age. Clodronate-liposomes obtained from Dr. N. van Rooijen (Vrije Universiteit, Amsterdam, Netherlands) were intravenously injected into mice twice every week, started in 4 weeks old mice, and continued for 3 months. The dose of clodronate-liposomes was 100µl during the first month and elevated to 150 100µl after that. The depletion efficacy was confirmed by detecting pulmonary macrophages with Flow Cytometry. Depletion of macrophages in these KA/KA-Lori.Ikkα mice could significantly reduce inflammation and prevent lung SCC developmrnt. This aim of this microarray assay is to identify differentially expressed genes among Wild type, KA/KA-Lori.Ikkα, and macophage-depleted KA/KA-Lori.Ikkα mice, which may highlight the important genes or parthways involved in inflammation-associated lung SCC carcinogenesis. Three samples were analyzed: 1. WT (lung tissue from wild type mouse); 2. KA2 (mixture tissue of lung SCC and tumor neighbor from KA/KA-Lori-Ikkα mouse ); 3. KAT (lung tissue from KA/KA-Lori-Ikkα mouse with macrophage depletion treatment)
Project description:Purpose: To study the alteration of whole transcriptome of Lewis lung carcinoma (LLC) cells after the decreasing of malignant properties of tumor by treatment of tumor-bearing mice with RNase A. Methods: Whole transcriptome profile of Lewis lung carcinoma before and after RNase A treatment were generated by deep sequencing using SOLiD 5.5. The sequence reads were mapped by Bioscope 1.3 software, differential expression was evaluated by Cufflinks v.2.0.1 package. Results: Difference in expression was found for 966 genes. Conclusions: Our study represents the first detailed analysis of alteration of transcriptome of Lewis lung carcinoma after the decrease of malignant prtoperties of the tumor (proliferation and invasion) by RNase A.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
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.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility. Gene expression was measured in whole testis from males aged 62-86 days. Samples include 190 first generation lab-bred male offspring of wild-caught mice from the Mus musculus musculus - M. m. domesticus hybrid zone.
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
Project description:Purpose: To study the alteration of whole transcriptome of Lewis lung carcinoma (LLC) cells after the decreasing of malignant properties of tumor by treatment of tumor-bearing mice with RNase A. Methods: Whole transcriptome profile of Lewis lung carcinoma before and after RNase A treatment were generated by deep sequencing using SOLiD 5.5. The sequence reads were mapped by Bioscope 1.3 software, differential expression was evaluated by Cufflinks v.2.0.1 package. Results: Difference in expression was found for 966 genes. Conclusions: Our study represents the first detailed analysis of alteration of transcriptome of Lewis lung carcinoma after the decrease of malignant prtoperties of the tumor (proliferation and invasion) by RNase A. Whole transcriptome profile of Lewis lung carcinoma before and after RNase A treatment were generated by deep sequencing using SOLiD 5.5.