Project description:Mutations of the thyrotropin receptor leading to constitutive activation of the cAMP cascade are responsible for the development of hot nodules, if arising in a somatic cell, and non-auto-immune hyperthyroidism, when occurring in a germinal cell. An animal model of constitutive activation of the thyroid cAMP cascade has been obtained by generating transgenic mice expressing the adenosine receptor (Tg-A2aR) under the control of the thyroglobulin promoter. These mice develop huge goiters and die prematurely due to hyperthyroidism induced cardiac failure. To identify new genes involved in the tumorigenic pathway of the thyroid, we designed a protocol using microarray technology to study the differential expression, between normal and transgenic thyroid, of +/- 13.000 genes. 360 genes or EST showed a strong modulation with background corrected values of fluorescence superior to 2 fold change. The modulated genes were classified according to their proposed gene ontology functions. Approximately half of them were upregulated. The function of the majority of these genes in thyroid physiology is still to be determined. Some of them, like IGF-I, IGF-BP3, IGF-BP5, may play an important role in the development of thyroid nodules through paracrine mechanisms. Keywords = Thyroid Keywords = Adenosine Receptor 2a Keywords: parallel sample
Project description:Mutations of the thyrotropin receptor leading to constitutive activation of the cAMP cascade are responsible for the development of hot nodules, if arising in a somatic cell, and non-auto-immune hyperthyroidism, when occurring in a germinal cell. An animal model of constitutive activation of the thyroid cAMP cascade has been obtained by generating transgenic mice expressing the adenosine receptor (Tg-A2aR) under the control of the thyroglobulin promoter. These mice develop huge goiters and die prematurely due to hyperthyroidism induced cardiac failure. To identify new genes involved in the tumorigenic pathway of the thyroid, we designed a protocol using microarray technology to study the differential expression, between normal and transgenic thyroid, of +/- 13.000 genes. 360 genes or EST showed a strong modulation with background corrected values of fluorescence superior to 2 fold change. The modulated genes were classified according to their proposed gene ontology functions. Approximately half of them were upregulated. The function of the majority of these genes in thyroid physiology is still to be determined. Some of them, like IGF-I, IGF-BP3, IGF-BP5, may play an important role in the development of thyroid nodules through paracrine mechanisms. Keywords = Thyroid Keywords = Adenosine Receptor 2a Keywords: parallel sample
Project description:Mutations of the thyrotropin receptor leading to constitutive activation of the cAMP cascade are responsible for the development of hot nodules, if arising in a somatic cell, and non-auto-immune hyperthyroidism, when occurring in a germinal cell. An animal model of constitutive activation of the thyroid cAMP cascade has been obtained by generating transgenic mice expressing the adenosine receptor (Tg-A2aR) under the control of the thyroglobulin promoter. These mice develop huge goiters and die prematurely due to hyperthyroidism induced cardiac failure. To identify new genes involved in the tumorigenic pathway of the thyroid, we designed a protocol using microarray technology to study the differential expression, between normal and transgenic thyroid, of +/- 13.000 genes. 360 genes or EST showed a strong modulation with background corrected values of fluorescence superior to 2 fold change. The modulated genes were classified according to their proposed gene ontology functions. Approximately half of them were upregulated. The function of the majority of these genes in thyroid physiology is still to be determined. Some of them, like IGF-I, IGF-BP3, IGF-BP5, may play an important role in the development of thyroid nodules through paracrine mechanisms. This study demonstrates the feasibility of sequentially after the cascade of events leading to the formation of benign tumors such as hot thyroid nodule or hyperfunctional goitre.
Project description:Mutations of the thyrotropin receptor leading to constitutive activation of the cAMP cascade are responsible for the development of hot nodules, if arising in a somatic cell, and non-auto-immune hyperthyroidism, when occurring in a germinal cell. An animal model of constitutive activation of the thyroid cAMP cascade has been obtained by generating transgenic mice expressing the adenosine receptor (Tg-A2aR) under the control of the thyroglobulin promoter. These mice develop huge goiters and die prematurely due to hyperthyroidism induced cardiac failure. To identify new genes involved in the tumorigenic pathway of the thyroid, we designed a protocol using microarray technology to study the differential expression, between normal and transgenic thyroid, of +/- 13.000 genes. 360 genes or EST showed a strong modulation with background corrected values of fluorescence superior to 2 fold change. The modulated genes were classified according to their proposed gene ontology functions. Approximately half of them were upregulated. The function of the majority of these genes in thyroid physiology is still to be determined. Some of them, like IGF-I, IGF-BP3, IGF-BP5, may play an important role in the development of thyroid nodules through paracrine mechanisms. This study demonstrates the feasibility of sequentially after the cascade of events leading to the formation of benign tumors such as hot thyroid nodule or hyperfunctional goitre. Keywords: other
Project description:Gene expression profile of splenic B cells (CD19+) from transgenic mice expressing the Epstein-Barr virus (EBV) latent membrane proteins (LMP) 1 and/or LMP2A. Freshly harvested primary B cells were profiled. B lymphocytes from transgenic LMP1, LMP2A, LMP1/2A mice and negative littermates were profiled from 6 month old adult mice; lymphoma cells were passaged in SCID mice and profiled for three LMP1 positive lymphomas and one negative lymphoma. 12 total samples. 4 transgenic B lymphocyte samples pooled from multiple biological replicates were hybridized to duplicate microarrays: LMP1 (pooled from 2 replicates), LMP2A (pooled from 3 replicates); LMP1/2A (pooled from 5 replicates), negative littermates (pooled from 4 replicates). 3 biological replicates of LMP1 lymphomas expressing high, medium and low levels of LMP1 and; 1 negative lymphoma was hybridized to 1 microarray chip. The reference sample consisted of 4 biological replicates of splenic B cells (CD19+) pooled from 4-7 month old non-transgenic Balb/c mice. The same reference was used for all hybridizations.
Project description:Gene expression profile of splenic B cells (CD19+) from transgenic mice expressing the Epstein-Barr virus (EBV) latent membrane proteins (LMP) 1 and/or LMP2A. Freshly harvested primary B cells were profiled. B lymphocytes from transgenic LMP1, LMP2A, LMP1/2A mice and negative littermates were profiled from 6 month old adult mice; lymphoma cells were passaged in SCID mice and profiled for three LMP1 positive lymphomas and one negative lymphoma.