Project description:T cell-specific overexpression of miR-185 caused a developmental block at DN3 stage of thymopoiesis. DN3 stage thymocytes were sorted from the wild type (C57BL/6) and miR-185 Tg mice, followed by total RNA isolation.
Project description:The noncluster homeodomain containing gene, HOX11/TLX1 (TLX1) is detected at the breakpoint of the t(10;14)(q24;q11) chromosome translocation in patients with T cell Acute Lymphoblastic leukemia (T-ALL). This translocation results in the inappropriate expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated in IgHµ-TLX1Tg mice, which developed mature B cell lymphoma after a long latency period suggesting the requirement of additional mutations to initiate malignancy. To determine whether dysregulation of genes involved in the DNA damage response contributed to tumor progression, we crossed IgHµ-TLX1Tg mice with PrkdcScid/Scid mice; To identify the molecular pathways dysregulated in the earliest stages of TLX1-induced transformation, we used Affimetrix microarrays to compare gene expression profiling of premaliganant thymocytes (6~8 weeks old): DN1, DN2 and DN3 stages from HOX11 transgenic PrkdcScid/Scid (HOXSCID) mice with the same stage thymocytes from the sex and age matched control PrkdcScid/Scid (SCID) mice. Expression analysis of IgH-TLX1TgPrkdcScid/Scid thymocytes revealed dysregulated expression of cell cycle, apoptotic, mitotic spindle and anaphase-promoting complex genes in double negative (DN) 2 and DN3 stage thymocytes. Moreover, DN1, DN2 and DN3 TLX1-expressing thymocytes showed downregulated expression of ribosomal and mitochondria ribosomal protein genes. Four groups of double mutant IgH-HOX11TgPrkdcScid/Scid mice and four groups of control PrkdcScid/Scid mice were sacrificed at the age of 6~8 weeks and the fresh thymocytes were FACS sorted by markers CD25 and CD44 to DN1, DN2 and DN3 stages. To minimize the sample variability caused by individual differences among animals, about 2 ~5 the same phenotype, stage and sex thymocytes were pooled (total 104 ~ 105 cells) and used as one sample each for RNA extraction and hybridization on Affymetrix microarrays.
Project description:The noncluster homeodomain containing gene, HOX11/TLX1 (TLX1) is detected at the breakpoint of the t(10;14)(q24;q11) chromosome translocation in patients with T cell Acute Lymphoblastic leukemia (T-ALL). This translocation results in the inappropriate expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated in IgHµ-TLX1Tg mice, which developed mature B cell lymphoma after a long latency period suggesting the requirement of additional mutations to initiate malignancy. To determine whether dysregulation of genes involved in the DNA damage response contributed to tumor progression, we crossed IgHµ-TLX1Tg mice with PrkdcScid/Scid mice; To identify the molecular pathways dysregulated in the earliest stages of TLX1-induced transformation, we used Affimetrix microarrays to compare gene expression profiling of premaliganant thymocytes (6~8 weeks old): DN1, DN2 and DN3 stages from HOX11 transgenic PrkdcScid/Scid (HOXSCID) mice with the same stage thymocytes from the sex and age matched control PrkdcScid/Scid (SCID) mice. Expression analysis of IgH-TLX1TgPrkdcScid/Scid thymocytes revealed dysregulated expression of cell cycle, apoptotic, mitotic spindle and anaphase-promoting complex genes in double negative (DN) 2 and DN3 stage thymocytes. Moreover, DN1, DN2 and DN3 TLX1-expressing thymocytes showed downregulated expression of ribosomal and mitochondria ribosomal protein genes.
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.