Advances in Experimental Medicine and Biology, 2009
To investigate the physiological role of menin, the protein product of the MEN1 gene, several gro... more To investigate the physiological role of menin, the protein product of the MEN1 gene, several groups have utilized gene targeting strategies to delete one or both copies of the mouse homolog Men1. Mice that are homozygous null for Men1 die during embryogenesis. Heterozygous Men1 mice are viable and develop many of the same types of tumors as humans with MEN1. In addition to conventional knockouts of Men1, tissue-specific elimination of menin using cre-lox has been achieved in pancreatic beta cells, anterior pituitary, parathyroid, liver, neural crest and bone marrow, with varying results that are dependent on cell context. In this chapter, we compare the phenotypes of the different conventional Men1 knockouts, detail the similarities and differences between Men1 pathogenesis in mice and humans and highlight results from recent crossbreeding studies between Men1 mutants and mice with null mutations in genes within the retinoblastoma pathway, including p18(Inc4c), p27(Kip1) and Rb. In addition, we discuss not only how the Men1 mutants have shed light on the role of menin in endocrine tumor suppression, but also how Men1 mutant mice have helped uncover previously unrecognized roles for menin in development, leukemogenesis and gestational diabetes.
Advances in Experimental Medicine and Biology, 2009
To investigate the physiological role of menin, the protein product of the MEN1 gene, several gro... more To investigate the physiological role of menin, the protein product of the MEN1 gene, several groups have utilized gene targeting strategies to delete one or both copies of the mouse homolog Men1. Mice that are homozygous null for Men1 die during embryogenesis. Heterozygous Men1 mice are viable and develop many of the same types of tumors as humans with MEN1. In addition to conventional knockouts of Men1, tissue-specific elimination of menin using cre-lox has been achieved in pancreatic beta cells, anterior pituitary, parathyroid, liver, neural crest and bone marrow, with varying results that are dependent on cell context. In this chapter, we compare the phenotypes of the different conventional Men1 knockouts, detail the similarities and differences between Men1 pathogenesis in mice and humans and highlight results from recent crossbreeding studies between Men1 mutants and mice with null mutations in genes within the retinoblastoma pathway, including p18(Inc4c), p27(Kip1) and Rb. In addition, we discuss not only how the Men1 mutants have shed light on the role of menin in endocrine tumor suppression, but also how Men1 mutant mice have helped uncover previously unrecognized roles for menin in development, leukemogenesis and gestational diabetes.
Colorectal Cancer Signature The mutations and genome aberrations that characterize cancer result ... more Colorectal Cancer Signature The mutations and genome aberrations that characterize cancer result in often dramatically altered gene and protein expression patterns. It is these altered expression patterns that directly and indirectly drive progression of the disease. In human primary colorectal cancer cells, Akhtar-Zaidi et al. (p. 736 , published online 12 April) analyzed the pattern of epigenetically modified chromatin at “enhancer” sequences that are known to be critical in the control of gene expression. An epigenetic enhancer signature was defined that was specifically associated with colorectal cancer cells.
CHD7 is a member of the chromodomain helicase DNA binding domain family of ATP-dependent chromati... more CHD7 is a member of the chromodomain helicase DNA binding domain family of ATP-dependent chromatin remodeling enzymes. De novo mutation of the CHD7 gene is a major cause of CHARGE syndrome, a genetic disease characterized by a complex constellation of birth defects (Coloboma of the eye, Heart defects, Atresia of the choanae, severe Retardation of growth and development, Genital abnormalities, and Ear abnormalities). To gain insight into the function of CHD7, we mapped the distribution of the CHD7 protein on chromatin using the approach of chromatin immunoprecipitation on tiled microarrays (ChIP-chip). These studies were performed in human colorectal carcinoma cells, human neuroblastoma cells, and mouse embryonic stem (ES) cells before and after differentiation into neural precursor cells. The results indicate that CHD7 localizes to discrete locations along chromatin that are specific to each cell type, and that the cell-specific binding of CHD7 correlates with a subset of histone H3...
Advances in Experimental Medicine and Biology, 2009
To investigate the physiological role of menin, the protein product of the MEN1 gene, several gro... more To investigate the physiological role of menin, the protein product of the MEN1 gene, several groups have utilized gene targeting strategies to delete one or both copies of the mouse homolog Men1. Mice that are homozygous null for Men1 die during embryogenesis. Heterozygous Men1 mice are viable and develop many of the same types of tumors as humans with MEN1. In addition to conventional knockouts of Men1, tissue-specific elimination of menin using cre-lox has been achieved in pancreatic beta cells, anterior pituitary, parathyroid, liver, neural crest and bone marrow, with varying results that are dependent on cell context. In this chapter, we compare the phenotypes of the different conventional Men1 knockouts, detail the similarities and differences between Men1 pathogenesis in mice and humans and highlight results from recent crossbreeding studies between Men1 mutants and mice with null mutations in genes within the retinoblastoma pathway, including p18(Inc4c), p27(Kip1) and Rb. In addition, we discuss not only how the Men1 mutants have shed light on the role of menin in endocrine tumor suppression, but also how Men1 mutant mice have helped uncover previously unrecognized roles for menin in development, leukemogenesis and gestational diabetes.
Advances in Experimental Medicine and Biology, 2009
To investigate the physiological role of menin, the protein product of the MEN1 gene, several gro... more To investigate the physiological role of menin, the protein product of the MEN1 gene, several groups have utilized gene targeting strategies to delete one or both copies of the mouse homolog Men1. Mice that are homozygous null for Men1 die during embryogenesis. Heterozygous Men1 mice are viable and develop many of the same types of tumors as humans with MEN1. In addition to conventional knockouts of Men1, tissue-specific elimination of menin using cre-lox has been achieved in pancreatic beta cells, anterior pituitary, parathyroid, liver, neural crest and bone marrow, with varying results that are dependent on cell context. In this chapter, we compare the phenotypes of the different conventional Men1 knockouts, detail the similarities and differences between Men1 pathogenesis in mice and humans and highlight results from recent crossbreeding studies between Men1 mutants and mice with null mutations in genes within the retinoblastoma pathway, including p18(Inc4c), p27(Kip1) and Rb. In addition, we discuss not only how the Men1 mutants have shed light on the role of menin in endocrine tumor suppression, but also how Men1 mutant mice have helped uncover previously unrecognized roles for menin in development, leukemogenesis and gestational diabetes.
Colorectal Cancer Signature The mutations and genome aberrations that characterize cancer result ... more Colorectal Cancer Signature The mutations and genome aberrations that characterize cancer result in often dramatically altered gene and protein expression patterns. It is these altered expression patterns that directly and indirectly drive progression of the disease. In human primary colorectal cancer cells, Akhtar-Zaidi et al. (p. 736 , published online 12 April) analyzed the pattern of epigenetically modified chromatin at “enhancer” sequences that are known to be critical in the control of gene expression. An epigenetic enhancer signature was defined that was specifically associated with colorectal cancer cells.
CHD7 is a member of the chromodomain helicase DNA binding domain family of ATP-dependent chromati... more CHD7 is a member of the chromodomain helicase DNA binding domain family of ATP-dependent chromatin remodeling enzymes. De novo mutation of the CHD7 gene is a major cause of CHARGE syndrome, a genetic disease characterized by a complex constellation of birth defects (Coloboma of the eye, Heart defects, Atresia of the choanae, severe Retardation of growth and development, Genital abnormalities, and Ear abnormalities). To gain insight into the function of CHD7, we mapped the distribution of the CHD7 protein on chromatin using the approach of chromatin immunoprecipitation on tiled microarrays (ChIP-chip). These studies were performed in human colorectal carcinoma cells, human neuroblastoma cells, and mouse embryonic stem (ES) cells before and after differentiation into neural precursor cells. The results indicate that CHD7 localizes to discrete locations along chromatin that are specific to each cell type, and that the cell-specific binding of CHD7 correlates with a subset of histone H3...
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