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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transactivation of the dopamine receptor 3 gene results in development of B-cell lymphoma in mice

ABSTRACT: Transactivation of the dopamine receptor 3 gene by a single provirus integration results in development of B-cell lymphoma in transgenic mice generated from retrovirally transduced embryonic stem cells. Gene transfer vectors based on retroviruses are commonly used in gene therapy applications because of their unique ability to integrate efficiently into host genomes. This ability also forms the basis of a transformation event that can be induced in transduced cells by transactivation of proto-oncogenes near the vector integration sites. Here, we report on the development of lymphoma in mice generated from embryonic stem cells transduced with an enhanced green fluorescent protein. The cells expressed B220, CD5, Mac1, and IgM on their surfaces and expressed transcription factors characteristic of B cell lymphoma. Importantly, each mouse had a single copy of the provirus in its genome; the copy was integrated into the second intron of the dopamine receptor 3 (D3) gene, and high-level expression of D3 was detected only in the lymphoma cells. Ectopic expression of D3 in murine marrow cells resulted in preferential proliferation of cells at the pre-B-cell stage in response to a D3-specific agonist, but this proliferation was not observed in vivo. Cells co-transduced with D3 and Bcl-xL genes had a phenotype similar to that of lymphoma in vivo, suggesting that the leukemogenesis induced by retroviral integration required âsecond hitâ mutations of additional genes. Two independently establisehd lymphoma cell lines and two control splenocyte samples were subjected to expression array analysis.

ORGANISM(S): Mus musculus

SUBMITTER: MASAFUMI ONODERA

PROVIDER: E-GEOD-20661 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transactivation of the dopamine receptor 3 gene results in development of B-cell lymphoma in mice

Project description:Transactivation of the dopamine receptor 3 gene by a single provirus integration results in development of B-cell lymphoma in transgenic mice generated from retrovirally transduced embryonic stem cells. Gene transfer vectors based on retroviruses are commonly used in gene therapy applications because of their unique ability to integrate efficiently into host genomes. This ability also forms the basis of a transformation event that can be induced in transduced cells by transactivation of proto-oncogenes near the vector integration sites. Here, we report on the development of lymphoma in mice generated from embryonic stem cells transduced with an enhanced green fluorescent protein. The cells expressed B220, CD5, Mac1, and IgM on their surfaces and expressed transcription factors characteristic of B cell lymphoma. Importantly, each mouse had a single copy of the provirus in its genome; the copy was integrated into the second intron of the dopamine receptor 3 (D3) gene, and high-level expression of D3 was detected only in the lymphoma cells. Ectopic expression of D3 in murine marrow cells resulted in preferential proliferation of cells at the pre-B-cell stage in response to a D3-specific agonist, but this proliferation was not observed in vivo. Cells co-transduced with D3 and Bcl-xL genes had a phenotype similar to that of lymphoma in vivo, suggesting that the leukemogenesis induced by retroviral integration required “second hit” mutations of additional genes.

2010-03-08 | GSE20661 | GEO

ATAC-seq of SLTM knockdown in HIV infected Jurkats

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2022-05-20 | GSE203235 | GEO

Disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism

Project description:The X-chromosomal dystonia parkinsonism syndrome (XDP) is associated with sequence changes within the TAF1/DYT3 multiple transcript system. While most sequence changes are intronic, one, DSC3, is located within an exon (d4). Transcribed exon d4 occurs as part of multiple splice variants. These variants include exons d3 and d4 spliced to exons of TAF1, and an independent transcript composed of exons d2-d4. Location of DSC3 in an exon (d4) and utilization of this exon in multiple splice variants suggests an important role of DSC3 in the pathogenesis of XDP. To test this hypothesis we transfected neuroblastoma cells with four expression constructs, including exons d2-d4 (d2-d4/wild-type (wt) and d2-d4/DSC3) and d3-d4 (d3-d4/wt and d3-d4/DSC3). Expression profiling revealed a dramatic effect of DSC3 on overall gene expression. 362 genes differ between cells containing d2-d4/wt and d2-d4/DSC3. Annotation clustering revealed high enrichment of genes related to dopamine metabolism, vesicular transport, synapse function, Ca++ metabolism, and oxidative stress. 211 genes were differentially expressed in d3-d4/wt vs. d3-d4/DSC3. Annotation clustering highlighted genes in signal transduction and cell-cell interaction. The data shows an important role of physiologically occurring transcript d2-d4 in normal brain function. Interference with this role by DSC3 is a likely pathological mechanism in XDP. Disturbance of dopamine function and of Ca++ metabolism can explain abnormal movement; loss of protection against reactive oxygen species may account for the neurodegenerative changes in XDP. Although d3-d4 also affect genes potentially related to neurodegenerative processes their physiologic role as splice variants of TAF1 awaits further exploration. We transfected neuroblastoma cells with four expression constructs, including exons d2-d4 (d2-d4/wild-type (wt) and d2-d4/DSC3) and d3-d4 (d3-d4/wt and d3-d4/DSC3).

2012-11-27 | E-GEOD-41157 | biostudies-arrayexpress

Mus musculus

Project description:Transactivation of the dopamine receptor 3 gene results in development of B-cell lymphoma in mice

| PRJNA124837 | ENA

Human activated Treg cells and retrovirally engineered Th cells, transduced with GARP, FOXP3 or control GFP vector

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2009-04-20 | E-GEOD-13234 | biostudies-arrayexpress

Disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism

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Expression profiling, Lin-9 depletion array in D3 mES cells

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2013-12-31 | E-GEOD-50916 | biostudies-arrayexpress

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Mac-1 cells with SATB1 silencing vs control Mac-1 cells

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