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Alterations in Cell Growth and Signaling in ErbB3 Binding Protein -1 (Ebp1) Deficient Mice

ABSTRACT: Background: The ErbB3 binding protein-1 (Ebp1) belongs to a family of DNA/RNA binding proteins implicated in cell growth, apoptosis and differentiation. However, the physiological role of Ebp1 in the whole organism is not known. Therefore, we generated Ebp1-deficient mice carrying a gene trap insertion in intron 2 of the Ebp1 (pa2g4) gene. Results: Ebp1 -/- mice were on average 30% smaller than wild type and heterozygous sex matched littermates. Growth retardation was apparent from Day 10 until Day 30. IGF-1 production and IGBP-3 and 4 protein levels were reduced in both embryo fibroblasts and adult knock-out mice. The proliferation of fibroblasts derived from Day 12.5 knock out embryos was also decreased as compared to that of wild type cells. Microarray expression analysis revealed changes in genes important in cell growth including members of the MAPK signal transduction pathway. In addition, the expression or activation of proliferation related genes such as AKT and the androgen receptor, previously demonstrated to be affected by Ebp1 expression in vitro, were altered in adult tissues. Conclusions: These results indicate that Ebp1 can affect growth in an animal model, but that the expression of proliferation related genes is cell and context specific. The Ebp1-/- mouse line represents a new in vivo model to investigate Ebp1 function in the whole organism.

ORGANISM(S): Mus musculus

PROVIDER: GSE13718 | GEO | 2009/03/31

SECONDARY ACCESSION(S): PRJNA110395

REPOSITORIES: GEO

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Alterations in Cell Growth and Signaling in ErbB3 Binding Protein -1 (Ebp1) Deficient Mice

Project description:Background: The ErbB3 binding protein-1 (Ebp1) belongs to a family of DNA/RNA binding proteins implicated in cell growth, apoptosis and differentiation. However, the physiological role of Ebp1 in the whole organism is not known. Therefore, we generated Ebp1-deficient mice carrying a gene trap insertion in intron 2 of the Ebp1 (pa2g4) gene. Results: Ebp1 -/- mice were on average 30% smaller than wild type and heterozygous sex matched littermates. Growth retardation was apparent from Day 10 until Day 30. IGF-1 production and IGBP-3 and 4 protein levels were reduced in both embryo fibroblasts and adult knock-out mice. The proliferation of fibroblasts derived from Day 12.5 knock out embryos was also decreased as compared to that of wild type cells. Microarray expression analysis revealed changes in genes important in cell growth including members of the MAPK signal transduction pathway. In addition, the expression or activation of proliferation related genes such as AKT and the androgen receptor, previously demonstrated to be affected by Ebp1 expression in vitro, were altered in adult tissues. Conclusions: These results indicate that Ebp1 can affect growth in an animal model, but that the expression of proliferation related genes is cell and context specific. The Ebp1-/- mouse line represents a new in vivo model to investigate Ebp1 function in the whole organism. Isolation of Mouse Embryo Fibroblasts (MEFS) and proliferation assays. Embryos (12.5 days) were minced and incubated in 0.25% trypsin and 5 U of DNAse I for 37º C for 30 min. Dulbecco’s MEM supplemented with 10% fetal bovine serum and penicillin and streptomycin were added to the cell suspension and cells centrifuged at 1000 rpm for 10 min. The pellet was resuspended in medium and cells were grown in MEM and passaged by trypsinization.

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