Search results for "Genetically Modified"
showing 10 items of 345 documents
IL-6 Signaling Promotes Tumor Growth in Colorectal Cancer
2004
Recent investigations support an important role for TGF-beta in the development of colorectal cancer. However, the molecular consequences of TGF-beta signaling in the colon remains incompletely understood. In a recent study in Immunity, we analyzed the role of TGF-beta in a murine model of colon cancer. Using transgenic mice overexpressing TGF-beta or a dominant negative TGF-beta receptor II under control of the CD2 minigene, we show that TGF-beta signaling in tumor infiltrating T lymphocytes regulates the growth of dysplastic colon epithelial cells, as determined by histology and a novel system for high resolution chromoendoscopy in vivo. At the molecular level, TGF-beta signaling in T cel…
Impairment of TGF-β signaling in T cells increases susceptibility to experimental autoimmune hepatitis in mice
2002
In autoimmune hepatitis, strong TGF-beta1 expression is found in the inflamed liver. TGF-beta overexpression may be part of a regulatory immune response attempting to suppress autoreactive T cells. To test this hypothesis, we determined whether impairment of TGF-beta signaling in T cells leads to increased susceptibility to experimental autoimmune hepatitis (EAH). Transgenic mice of strain FVB/N were generated expressing a dominant-negative TGF-beta type II receptor in T cells under the control of the human CD2 promoter/locus control region. On induction of EAH, transgenic mice showed markedly increased portal and periportal leukocytic infiltrations with hepatocellular necroses compared wit…
Astrocytic alterations in interleukin-6/Soluble interleukin-6 receptor alpha double-transgenic mice.
2000
Interleukin-6 (IL-6), a major cytokine with diverse effects on cells mainly of the immune and hematopoietic systems, has been linked to several neurological disorders such as acquired immune deficiency syndrome dementia, multiple sclerosis, and Alzheimer's disease. Central nervous system (CNS)-specific expression of IL-6 caused neurodegeneration, massive gliosis, and vascular proliferation in transgenic mice. However, the effects of systemically circulating IL-6 and its receptor IL-6Ralpha on the CNS are unknown. IL-6Ralpha is the specific component of the IL-6 receptor system and hence an important co-factor of IL-6. IL-6Ralpha is bioactive in a membrane-bound and in a soluble (s) form. We…
Profilin1 activity in cerebellar granule neurons is required for radial migration in vivo.
2014
Neuron migration defects are an important aspect of human neuropathies. The underlying molecular mechanisms of such migration defects are largely unknown. Actin dynamics has been recognized as an important determinant of neuronal migration, and we recently found that the actin-binding protein profilin1 is relevant for radial migration of cerebellar granule neurons (CGN). As the exploited brain-specific mutants lacked profilin1 in both neurons and glial cells, it remained unknown whether profilin1 activity in CGN is relevant for CGN migration in vivo. To test this, we capitalized on a transgenic mouse line that expresses a tamoxifen-inducible Cre variant in CGN, but no other cerebellar cell …
A Transgenic Mouse Model of Inducible Macrophage Depletion
2009
Whether the wound macrophage is a key regulatory inflammatory cell type in skin repair has been a matter of debate. A transgenic mouse model mediating inducible macrophage depletion during skin repair has not been used to date to address this question. Here, we specifically rendered the monocyte/macrophage leukocyte lineage sensitive to diphtheria toxin by expressing the lysozyme M promoter-driven, Cre-mediated excision of a transcriptional STOP cassette from the simian DT receptor gene in mice (lysM-Cre/DTR). Application of diphtheria toxin to lysM-Cre/DTR mice led to a rapid reduction in both skin tissue and wound macrophage numbers at sites of injury. Macrophage-depleted mice revealed a …
Defective insulin secretory response to intravenous glucose in C57Bl/6J compared to C57Bl/6N mice
2014
Objective: The C57Bl/6J (Bl/6J) mouse is the most widely used strain in metabolic research. This strain carries a mutation in nicotinamide nucleotide transhydrogenase (Nnt), a mitochondrial enzyme involved in NADPH production, which has been suggested to lead to glucose intolerance and beta-cell dysfunction. However, recent reports comparing Bl/6J to Bl/6N (carrying the wild-type Nnt allele) under normal diet have led to conflicting results using glucose tolerance tests. Thus, we assessed glucose-stimulated insulin secretion (GSIS), insulin sensitivity, clearance and central glucose-induced insulin secretion in Bl/6J and N mice using gold-standard methodologies. Methods: GSIS was measured u…
Inhibition of the HER2 pathway by n-3 polyunsaturated fatty acids prevents breast cancer in fat-1 transgenic mice
2013
Overexpression of the tyrosine kinase receptor, ErbB2/HER2/Neu, occurs in 25–30% of invasive breast cancer (BC) with poor patient prognosis. Due to confounding factors, inconsistencies still remain regarding the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on BC. We therefore evaluated whether fat-1 transgenic mice, endogenously synthesizing n-3 PUFAs from n-6 PUFAs, were protected against BC development, and we then aimed to study in vivo a mechanism potentially involved in such protection. E0771 BC cells were implanted into fat-1 and wild-type (WT) mice. After tumorigenesis examination, we analyzed the expression of proteins involved in the HER2 signaling pathway and lipi…
n-3 polyunsaturated fatty acids and HER2-positive breast cancer: interest of the fat-1 transgenic mouse model over conventional dietary supplementati…
2013
Overexpression of the tyrosine kinase receptor ErbB2/HER2/Neu, occurs in 25%-30% of invasive breast cancer (BC) with poor patient prognosis. Even if numerous studies have shown prevention of breast cancer by n-3 fatty acid intake, the experimental conditions under which n-3 fatty acids exert their protective effect have been variable from study to study, preventing unifying conclusions. Due to confounding factors, inconsistencies still remain regarding protective effects of n-3 polyunsaturated fatty acids (PUFA) on BC. When animals are fed with dietary supplementation in n-3 fatty acids (the traditional approach to modify tissue content and decrease the n-6/n-3 ratio) complex dietary intera…
Glycosylation deficiency at either one of the two glycan attachment sites of cellular prion protein preserves susceptibility to bovine spongiform enc…
2004
The conversion into abnormally folded prion protein (PrP) plays a key role in prion diseases. PrP(C) carries two N-linked glycan chains at amino acid residues 180 and 196 (mouse). Previous in vitro data indicated that the conversion process may not require glycosylation of PrP. However, it is conceivable that these glycans function as intermolecular binding sites during the de novo infection of cells on susceptible organisms and/or play a role for the interaction of both PrP isoforms. Such receptor-like properties could contribute to the formation of specific prion strains. However, in earlier studies, mutations at the glycosylation sites of PrP led to intracellular trafficking abnormalitie…
Constitutive and inducible expression of CYP enzymes in immortal hepatocytes derived from SV40 transgenic mice
2003
1. The expression of liver-specific transcription factors and cytochrome P450 (CYP) enzymes have been studied in three new hepatocyte-like cell lines derived from SV Delta 202 transgenic mice: AMH-Delta 202 (adult mouse hepatocytes), TAMH-Delta 202 (tumour-derived adult mouse hepatocytes) and NMH-Delta 202 (newborn mouse hepatocytes). 2. mRNA levels of liver-enriched transcription factors such as D-element binding protein (DBP), liver-enriched transcription activating protein (LAP) and the hepatic nuclear factors (HNF) 1, 2 and 3 in all Delta 202 transgenic hepatocyte lines were similar to those in the wild-type liver and in primary mouse hepatocytes. 3. Analysis of basal CYP activities and…