Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A herpes simplex virus (HSV) vector in which the mammalian promoter for neuron-specific enolase (NSE) controls expression of a marker gene was analyzed for its ability to drive expression of this foreign gene in culture and in vivo. In cultured cells, the vector appeared to give neuron-specific expression. Introduction of 10(6) pfu of the virus into the adult rat caudate nucleus by stereotactic injection was not toxic to the animals and yielded beta-galactosidase (beta-gal)-positive neurons for at least 30 days after viral inoculation. This recombinant herpes virus vector is the first described to use a mammalian promoter to yield extended expression of a foreign gene product in the adult mammalian central nervous system (CNS).
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PMID:Gene transfer into mammalian central nervous system using herpes virus vectors: extended expression of bacterial lacZ in neurons using the neuron-specific enolase promoter. 132 93

To gain insights into transcription factors defining neuronal identity, we generated transgenic mice carrying a 1.8 kb rat neuron-specific enolase (NSE) promoter fragment fused to an E. coli lacZ gene. Four of seven transgenic families expressed transgene RNA in the nervous system but not in most other tissues. Histochemical analysis of adult brain from the two lines with highest lacZ mRNA levels showed neuron-specific, pan-neuronal beta-galactosidase activity. Developmental RNA and histochemical analyses showed parallel onset of transgene and endogenous NSE gene expression in various neuronal cell types, although the magnitude of NSE mRNA accumulation later in development was not matched by the transgene. These results suggest that cis-acting regulatory elements, subject to neuron-specific control, are located within 1.8 kb upstream from the NSE gene.
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PMID:Transgenic mice expressing beta-galactosidase in mature neurons under neuron-specific enolase promoter control. 211 14

After transplantation of embryonic retinal cells to injured adult retina, it is often difficult to distinguish donor from host cells. To overcome this problem, two methods were applied: labelling donor cells with the nuclear marker bromodeoxyuridine (BrdU) and use of transgenic donor tissue. BrdU was injected into timed-pregnant rats on 2 or 3 consecutive days. The donor embryos were taken 1-4 days later for transplantation. The BrdU-labelled donor tissue was examined in transplants sampled up to 1 year after grafting. Labelled donor cells were specifically identified in the transplants and in the interface with the adjacent host retina. The varying intensities of cell labelling indicated differences in the initial uptake of BrdU in the S-phase, or the dilution of the label by cell divisions after BrdU injection. The best labelled cells were presumably the ones that stopped dividing shortly after injection of BrdU. As controls, the normal development of BrdU-labelled retinas from the offspring of females that had been BrdU-injected at E16 and E17 and not used for transplantation was studied. Near the time of birth, clones of labelled cells were radially distributed. In the mature retina, labelled cells were seen in all retinal layers. Embryonic retina derived from transgenic (NSE-lacZ) mice was transplanted to 'nude', immunodeficient rats (xenografts). These transgenic mice contain the Escherichia coli beta-galactosidase gene, coupled to the promoter for neuron-specific enolase (NSE). Thus, all retinal donor cells that contain NSE could be identified by histochemistry or immunohistochemistry. The donor cells expressing the transgene could be detected several months after transplantation.
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PMID:Transplantation of embryonic retinal donor cells labelled with BrdU or carrying a genetic marker to adult retina. 758 18

Mouse embryonic stem (ES) cells were transfected with a plasmid composed of an E. coli lacZ gene fused to 1.8 kb of rat neuron-specific enolase (NSE) promoter sequences. While this reporter construct had been shown previously to function exclusively in postmitotic neurons and neuro-endocrine cells of transgenic mice, stably transfected ES cell clones unexpectedly displayed beta-galactosidase (beta-Gal) activity in the undifferentiated state. This transcriptional activity of the heterologous NSE promoter was confirmed by the identification of endogenous NSE mRNA in undifferentiated ES cells, mouse morulae and blastocysts. NSE protein, however, could not be found in undifferentiated ES cells. Interestingly, in ES cells which were cultured for 7 days under differentiation conditions in vitro, beta-Gal activity decreased to basal levels consistent with the parallel down-regulation of endogenous NSE mRNA. In contrast, prolonged culture of ES cells under differentiation conditions led to the reappearance of NSE mRNA and beta-Gal activity after 17 days. Significant increases in beta-Gal activity were also observed in ES cells which were cultured either on dishes coated with attachment factors such as laminin and gelatin or in the presence of nerve growth factor (NGF). These results suggest that i) transcriptional control mechanisms regulating neuronal gene expression are present at early developmental stages in the mouse and ii) ES cells provide a useful in vitro model system for the analysis of developmentally regulated cellular and molecular events coupled to neuron-specific enolase promoter activity.
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PMID:Transcriptional activity of the neuron-specific enolase (NSE) promoter in murine embryonic stem (ES) cells and preimplantation embryos. 792 88

1. Herpesvirus infection with genetically engineered vectors is a way to deliver foreign gene products to various cell populations in culture and in vivo. Selective neuronal gene expression can be achieved using the neuron-specific enolase (NSE) promoter regulating expression of a transgene placed in and delivered by a herpesvirus vector. 2. We sought to determine the anatomical specificity and efficiency of herpesvirus-mediated gene transfer into the rat brain following placement of virus particles carrying a transgene (lacZ) under control of the NSE promoter. The virus utilized was thymidine kinase (TK) deficient and therefore replication deficient in the brain. 3. Infusion of 10(6) plaque-forming units of virus into the striatum caused a limited number of striatal neurons to express the lacZ transgene mRNA and protein product 7 days postinfection. In addition, small numbers of neurons expressing the transgene mRNA and protein were found ipsilateral to the viral injection in the frontal cortex, substantia nigra pars compacta, and thalamus. Neurons at these anatomic loci project directly to the striatal injection site. No other cells within the brains of injected animals expressed the lacZ gene. 4. While this herpesvirus NSE vector was capable of introducing novel functional genetic information into postmitotic neurons within defined neuroanatomic constraints, the numbers of neurons expressing detectable levels of beta-galactosidase was minimal. The calculated efficiency of delivery and transgene expression at 7 days postinfection was 1 transgenic neuron per 10(4) virus particles infused. 5. We conclude that NSE probably is not an optimal promoter for use in gene delivery to CNS neurons in herpesvirus vectors and that the efficacy of gene delivery using other neuron-specific promoters placed at various sites in the herpes viral genome needs to be explored.
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PMID:Herpesvirus-mediated gene delivery into the rat brain: specificity and efficiency of the neuron-specific enolase promoter. 811 22

An androgen-repressed human prostate cancer cell line, ARCaP, was established and characterized. This cell line was derived from the ascites fluid of a patient with advanced metastatic disease. In contrast to the behavior of androgen-dependent LNCaP and its androgen-independent C4-2 subline, androgen and estrogen suppress the growth of ARCaP cells in a dose-dependent manner in vivo and in vitro. ARCaP is tumorigenic and highly metastatic. It metastasizes to the lymph node, lung, pancreas, liver, kidney, and bone, and forms ascites fluid in athymic hosts. ARCaP cells express low levels of androgen receptor mRNA and prostate-specific antigen mRNA and protein. Immunohistochemical staining shows that ARCaP cells stain intensely for epidermal growth factor receptor, c-erb B2/neu, and c-erb B3. Staining is negative for chromogranin A and positive for bombesin, serotonin, neuron-specific enolase, and the c-met protooncogene (a hepatic growth factor/scatter factor receptor). ARCaP cells also secrete high levels of gelatinase A and B and some stromelysin, which suggests that this cell line may contain markers representing invasive adenocarcinoma with selective neuronendocrine phenotypes. Along with its repression of growth, androgen is also found to repress the expression of prostate-specific antigen in ARCaP cells as detected by a prostate-specific antigen promoter-beta-galactosidase reporter assay. Our results suggest that the androgen-repressed state may be central to prostate cancer progression and that advanced prostate cancer can progress from an androgen-independent to an androgen-repressed state.
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PMID:Androgen-repressed phenotype in human prostate cancer. 898 79

Brain disorders induced by congenital cytomegalovirus (CMV) infection may appear at a later time after birth as a consequence of persistent infection and/or the activation of a latent infection of the neural cells. We have analyzed the infection dynamics of the neural cells in the neonatal mouse brains infected with murine CMV (MCMV) in the late stage of gestation. First we prepared a rat monoclonal antibody to the major immediate-early (IE)-89K antigen and then used the antibody for comparison of the expression of early and late viral genes in the developing mouse brains. The cells expressing the IE-89K antigen were mostly localized in the ventricular and subventricular zones and were preferentially double stained with anti-glial fibrillary acidic protein and anti-nestin antibodies. In contrast, the cells expressing the early nuclear antigen, detected by the monoclonal antibody D5, were diffusely distributed in the cortex and the hippocampus and were mostly double labeled with anti-neuron-specific enolase antibody. In neonatal mouse brains infected congenitally with recombinant MCMV, which expressed lacZ as a late gene, the number of the early nuclear antigen-positive cells was much higher than that of the beta-galactosidase-expressing cells, the number of which was almost the same as that of the IE-89K antigen-positive cells. In addition, the distribution of viral DNA-rich cells detected by DNA-DNA hybridization was similar to that of the IE-89K antigen-positive cells. These results suggest that CMV may persistently infect neuronal cells, whereas lytic infection may preferentially occur in the glial cells in the developing brain.
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PMID:Differential expression of the immediate-early and early antigens in neuronal and glial cells of developing mouse brains infected with murine cytomegalovirus. 935 59

Neural stem cells persist in the adult brain subventricular zone (SVZ). These cells generate a large number of new neurons that migrate to the olfactory bulb, where they complete their differentiation. Here, we transplanted cells carrying beta-galactosidase under the control of neuron-specific enolase promoter (NSE::LacZ) from the SVZ of adult mice into the striatum cortex and olfactory bulb, with or without an excitotoxin lesion. Between 2 and 8 weeks after transplantation, grafted cells were present in the recipient regions, but extensive migration and differentiation into mature neurons of grafted cells were only observed in the olfactory bulb. Clusters of graft-derived neuroblasts forming chain-like structures were observed within or close to the grated sites in the cortex and striatum; electron microscopy confirmed that graft-derived cells in the olfactory bulb and a small number in the striatum were neurons. Surprisingly, most of the cells expressing NSE::LacZ outside the olfactory bulb were astrocytes. We conclude that primary precursors from the SVZ migrate and differentiate effectively only within the environment of the olfactory bulb. Only limited survival and differentiation were observed in other brain regions studied.
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PMID:Adult-derived neural precursors transplanted into multiple regions in the adult brain. 1058 39

The present study investigated cerebrospinal fluid (CSF) biomarkers for estimating degeneration of the central nervous system (CNS) in experimental dogs with GM1 gangliosidosis and preliminarily evaluated the efficacy of long-term glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid beta-galactosidase activity. Pathogenesis of GM1 gangliosidosis may include neuronal apoptosis and abnormal axoplasmic transport and inflammatory response, which are perhaps consequent to massive neuronal storage of GM1 ganglioside. In the present study, we assessed some possible CSF biomarkers, such as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and myelin basic protein (MBP). Periodic studies demonstrated that GM1 ganglioside concentration, activities of AST and LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs with GM1 gangliosidosis than those in control dogs, and their changes were well related with the months of age and clinical course. In conclusion, GM1 ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of novel therapies proposed for this disease. In addition, we preliminarily treated an affected dog with long-term oral administration of prednisolone and evaluated the efficacy of this therapeutic trial using CSF biomarkers determined in the present study. However, this treatment did not change either the clinical course or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy would not be effective for treating GM1 gangliosidosis.
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PMID:Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis: possible use for assessment of a therapeutic regimen. 1719 62

Serum-free mouse embryo (SFME) cells are an epidermal growth factor (EGF)-dependent established line derived from brains of 16-d-old Balb/c mouse embryos. SFME cells grow indefinitely in serum-free medium without replicative senescence, chromosomal abnormalities, or malignant transformation. SFME cells express nestin, a neural stem cell marker, under serum-free conditions. Exposure to serum or transforming growth factor beta (TGF-beta) leads to a marked increase in differentiation toward the astrocytic lineage with expression of glial fibrillary acidic protein and other astrocyte markers. In this study, we show that treatment of SFME cells with bone morphogenetic protein-4 (BMP-4), another member of the TGF-beta family, led to differentiation toward a neuronal lineage under conditions of low mitogenic stimulation (0.5 ng/mL) by EGF and fibroblast growth factor. Maximum mitogenic stimulation with 50 ng/mL EGF blocked the BMP-4 effect on neuronal differentiation, but did not block TGF-beta-induced expression of markers of the astrocytic lineage. BMP-4 treatment also enhanced the activity of the neuron-specific enolase (NSE) promoter in SFME-NSE-lacZ cells that carry the gene for bacterial beta-galactosidase under the control of the NSE promoter. Extended BMP-4 treatment caused SFME cells to express a neuronal phenotype synthesizing gamma-aminobutyric acid. These results indicate that SFME cells have the capacity to generate both neurons and astrocytes in vitro, which resemble the behavior of EGF-dependent multipotential stem cells in the central nervous system, and establish a relationship between effects of BMP-4 and degree of mitogenic stimulation by other peptide growth factors.
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PMID:Mitogen limitation and bone morphogenetic protein-4 promote neurogenesis in SFME cells, an EGF-dependent neural stem cell line. 1905 72


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