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)

Dynamic expression patterns of four retinoid-metabolizing enzymes create rapidly changing retinoic acid (RA) patterns in the emerging eye anlage of the mouse. First, a RA-rich ventral zone is set up, then a RA-poor dorsal zone, and finally a tripartite organization consisting of dorsal and ventral RA-rich zones separated by a horizontal RA-poor stripe. This subdivision of the retina into three RA concentration zones is directly visible as beta-galactosidase labeling patterns in retinas of RA-reporter mice. Because the axons of retinal ganglion cells transport the reporter product anterogradely, the central projections from dorsal and ventral retina can be visualized as two heavily labeled axon bundles. Comparisons of the axonal labeling with physiologic recordings of visual topography in the adult mouse show that the labeled axons represent the upper and the lower visual fields. The RA-poor stripe develops into a broad horizontal zone of higher visual acuity. Comparisons of the retina labeling with eye-muscle insertions show that the axis of the RA pattern lines up with the dorsoventral axis of the oculomotor system. These observations indicate that the dorsoventral axis of the embryonic eye anlage determines the functional coordinates of both vision and eye movements in the adult.
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PMID:Retinoic acid in the formation of the dorsoventral retina and its central projections. 1083 33

Tracing neural connectivity is important in understanding the intricacy of the nervous system as this represents the functional unit throughout the system. Here, we provide evidence that beta-galactosidase (beta-gal) linked to the N-terminal axonal translocation signal of GAP-43 provides a reproducible and versatile reporter system for analyzing the developing nervous system in vivo. When expressed by the GAP-43 promoter in transgenic mice, the fusion protein is detected equally within the developing axons of the peripheral and the central nervous systems, directly reflecting the promoter activity.
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PMID:GAP-43 N-terminal translocation signal targets beta-galactosidase to developing axons in a pan-neuronal transgenic mouse line. 1083 98

Proteolipid protein (PLP) and its alternatively spliced isoform, DM20, are the main intrinsic membrane proteins of compact myelin in the CNS. PLP and DM20 are also expressed by Schwann cells, the myelin-forming cells in the PNS, and are necessary for normal PNS function in humans. We have investigated the expression of PLP in the PNS by examining transgenic mice expressing a LacZ transgene under the control of the PLP promoter. In these animals, myelinating Schwann cells expressed beta-galactosidase more prominently than nonmyelinating Schwann cells. PLP/DM20 mRNA levels, but not those of LacZ mRNA, increased during sciatic nerve development and decreased after axotomy, with resultant Wallerian degeneration. PLP/DM20 transcription rates, in nuclear run off experiments, however, did not increase in developing rat sciatic nerve despite robust increases in PLP/DM20 mRNA levels during the same period. In RNAse protection studies, PLP mRNA levels fell to undetectable levels following nerve transection whereas levels of DM20 were essentially unchanged despite both being transcribed from the same promoter. Finally, cotransfection studies demonstrated that PLP-GFP, but not DM20-GFP mRNA is down-regulated in Schwann cells cultured in the absence of forskolin. Taken together these data demonstrate that steady state levels of PLP mRNA are regulated at a posttranscriptional level in Schwann cells, and that this regulation is mediated by Schwann cell-axonal contact. Since the difference between these two mRNAs is a 105-bp sequence in PLP and not in DM20, this sequence is likely to play a role in the regulation of PLP mRNA.
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PMID:Proteolipid protein mRNA stability is regulated by axonal contact in the rodent peripheral nervous system. 1088 Jan 28

The gene for the human poliovirus receptor (hPVR/CD155) is the founding member of a new family of genes encoding proteins belonging to the immunoglobulin superfamily. To determine whether CD155 is expressed during mammalian development, we have made use of the previously characterized promoter of the CD155 gene and generated mice transgenic for a CD155 promoter-driven beta-galactosidase reporter gene. Expression of the reporter gene in transgenic embryos was observed during midgestation in anterior midline structures of the developing central nervous system and in the neuroretina. During that period, reporter gene expression appeared within the notochord and floor plate along the entire spinal cord reaching into the caudal diencephalon. In addition, transgene expression was observed in axonal projections emanating from retinal ganglion cells forming the optic nerve to reach the future region of the optic chiasm. Analysis of expression of CD155 during human embryonic development confirmed the distribution of reporter gene expression specified by CD155 promoter activity. The anatomical distribution of CD155 promoter activity during embryogenesis matches that of transacting factors previously identified to regulate transcription of the CD155 gene. Expression of CD155 within embryonic structures giving rise to spinal cord anterior horn motor neurons may explain the restrictive host cell tropism of poliovirus for this cellular compartment of the CNS.
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PMID:Expression of the human poliovirus receptor/CD155 gene during development of the central nervous system: implications for the pathogenesis of poliomyelitis. 1091 95

Herpes simplex virus type 1 (HSV-1) is a human, neurotropic pathogen which also can infect experimental animals. Much interest has been focused on genetic modification of HSV-1 so that it can be used as a vector for gene delivery and for tracing neuronal connections. For expression of a foreign gene inserted into the HSV-1 genome, both the site of insertion and the promoter activity are important. We have used a previously described HSV-1 vector, KOS/58, to demonstrate that the beta-galactosidase gene inserted together with a neurofilament L promoter into the coding region of the glycoprotein C (gC) gene is under the control of the foreign promoter rather than under that of the gC gene. This was performed by isolation of RNA from infected, neuron-like PC12 cells and Northern blotting using probes from various regions of the modified part of the genome. The vector was then inoculated in the cornea, subconjunctivally, or into the anterior chamber of the mouse eye. Whole mounts of the trigeminal, superior cervical and pterygopalatine ganglions were stained for beta-galactosidase. The localization of labelled neurons was consistent with retrograde axonal transport as the principal way of neuronal infection indicating that KOS/58 could be used as a retrograde tracer. The position of the labelled cells suggests a somatotopic organization of the mouse trigeminal and superior cervical ganglion similar to that of rats and rabbits.
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PMID:A herpes simplex virus type 1 vector as marker for retrograde neuronal tracing: characterization of lacZ transcription and localization of labelled neuronal cells in sensory and autonomic ganglia after inoculation of the anterior segment of the eye. 1104 85

Previously, we observed that injection of an adenoviral (Ad) vector expressing glial cell line-derived neurotrophic factor (GDNF) into the striatum, but not the substantia nigra (SN), prior to a partial 6-OHDA lesion protects dopaminergic (DA) neuronal function and prevents the development of behavioral impairment in the aged rat. This suggests that striatal injection of AdGDNF maintains nigrostriatal function either by protecting DA terminals or by stimulating axonal sprouting to the denervated striatum. To distinguish between these possible mechanisms, the present study examines the effect of GDNF gene delivery on molecular markers of DA terminals and neuronal sprouting in the aged (20 month) rat brain. AdGDNF or a control vector coding for beta-galactosidase (AdLacZ) was injected unilaterally into either the striatum or the SN. One week later, rats received a unilateral intrastriatal injection of 6-OHDA on the side of vector injection. Two weeks postlesion, rats injected with AdGDNF into either the striatum or the SN exhibited a reduction in the area of striatal denervation and increased binding of the DA transporter ligand [(125)I]IPCIT in the lesioned striatum compared to control animals. Furthermore, injections of AdGDNF into the striatum, but not the SN, increased levels of tyrosine hydroxylase mRNA in lesioned DA neurons in the SN and prevented the development of amphetamine-induced rotational asymmetry. In contrast, the level of T1 alpha-tubulin mRNA, a marker of neuronal sprouting, was not increased in lesioned DA neurons in the SN following injection of AdGDNF either into the striatum or into the SN. These results suggest that GDNF gene delivery prior to a partial lesion ameliorates damage caused by 6-OHDA in aged rats by inhibiting the degeneration of DA terminals rather than by inducing sprouting of nigrostriatal axons.
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PMID:Glial cell line-derived neurotrophic factor (GDNF) gene delivery protects dopaminergic terminals from degeneration. 1131 61

Three Alaskan Huskies, two females and one male, were diagnosed with GM1-gangliosidosis. Clinically, diseased animals exhibited proportional dwarfism and developed progressive neurologic impairment with signs of cerebellar dysfunction at the age of 5-7 months. Skeletal lesions characterized by retarded enchondral ossification of vertebral epiphyses were revealed by radiographs of the male dog at 5.5 months of age. Histologic examination of the central nervous system (CNS) revealed that most neurons were enlarged with a foamy to granular cytoplasm due to tightly packed vacuoles that displaced the Nissl substance. Vacuoles in paraffin-embedded sections stained positively with Luxol fast blue and Grocott's method, and in frozen sections vacuoles were periodic acid-Schiff positive. Foamy vacuolation also occurred within neurons of the autonomic ganglia. Extracerebral cells such as macrophages and peripheral lymphocytes also displayed foamy cytoplasm and vacuolation. In the CNS of diseased animals, a mild demyelination and axonal degeneration was accompanied by a significant astrogliosis (P < 0.05) in the gray matter as compared with age- and sex-matched control dogs. There was also a significant loss (P < 0.05) of oligodendrocytes in the gray and white matter of affected animals as compared with controls. Ultrastructurally, the neuronal storage material consisted of numerous circular to concentric whorls of lamellated membranes or stacks of membranes in parallel arrays. GM1-gangliosidosis in Alaskan Huskies resembles beta-galactosidase deficiency in other canine breeds, and these CNS disorders may be a consequence of neuronal storage and disturbed myelin processing.
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PMID:GM1-gangliosidosis in Alaskan huskies: clinical and pathologic findings. 1135 58

Reporter gene expression in the olfactory epithelium of H-lacZ6 transgenic mice mimics the cell-selective expression pattern known for some odorant receptor genes. The transgene construct in these mice consists of the lacZ coding region, driven by the proximal olfactory marker protein (OMP) gene promoter, and shows expression in a zonally confined subpopulation of olfactory neurons. To address mechanisms underlying the odorant receptor-like expression pattern of the lacZ construct, we analyzed the transgene-flanking region and identified OR-Z6, the first cloned odorant receptor gene that maps to mouse chromosome 6. OR-Z6 bears the highest sequence similarity (85%) to a human odorant receptor gene at the syntenic location on human chromosome 7. We analyzed the expression pattern of OR-Z6 in olfactory tissues of H-lacZ6 mice and show that it bears strong similarities to that mapped for beta-galactosidase. Expression of both genes in olfactory neurons is primarily restricted to the same medial subregion of the olfactory epithelium. Axons from both neuronal subpopulations project to the same ventromedial aspect of the anterior olfactory bulbs. Furthermore, colocalization analyses in H-lacZ6 mice demonstrate that OR-Z6-reactive glomeruli receive axonal input from lacZ-positive neurons as well. These results suggest that the expression of both genes is coordinated and that transgene expression in H-lacZ6 mice is regulated by locus-dependent mechanisms.
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PMID:The OMP-lacZ transgene mimics the unusual expression pattern of OR-Z6, a new odorant receptor gene on mouse chromosome 6: implication for locus-dependent gene expression. 1142 91

Lesioned axons within the dorsal roots fail to regenerate through the peripheral nerve transition zone and into the spinal cord. This regenerative failure leads to a persistent loss of sensory function. To induce axonal growth across this barrier, we used recombinant adenovirus to express fibroblast growth factor-2 (FGF2), nerve growth factor (NGF), L1 cell adhesion molecule (L1), or beta-galactosidase (LacZ) within the endogenous glia of the dorsal spinal cord 16 d after injury. Expression of either FGF2 or NGF, but not L1 or LacZ, induced robust axonal regeneration into normal as well as ectopic locations within the dorsal spinal cord. This regeneration led to near-normal recovery of thermal sensory function. Functional recovery and the majority of regenerating axons within the dorsal horn disappeared with recutting of the sensory roots. Injections of adenovirus encoding NGF, but not FGF2, also resulted in extensive sprouting of noninjured sensory axons, which we previously demonstrated could cause hyperalgesia and chronic pain. Thus, neurotrophic factor gene therapy administered as late as 16 d after injury may serve as a useful treatment to elicit recovery after dorsal root avulsion; however, the choice of neurotrophin is important to induce selective regeneration of damaged axons.
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PMID:Functional regeneration of chronically injured sensory afferents into adult spinal cord after neurotrophin gene therapy. 1160 29

Current surgical strategies for repair of critical nerves involves the transfer of normal donor nerve from an uninjured body location. One possible alternative to autogenous tissue replacement is the development of engineered constructs to replace those elements necessary for axonal proliferation. Delivery of growth factors is one strategy to enhance synthetic nerve constructs. Thus, this study focused on the delivery of nerve growth factor (NGF) by genetic engineering to begin approaching the microenvironment dictated, in part, by Schwann's cells. Rat dermal fibroblasts (DFBs) were modified genetically to release rat NGF. The reporter gene LacZ was used to assess the optimum nonviral transfection method commercially available before NGF transfection. FuGENE6 provided the optimum transfection efficiency (24% maximum, 20.1 +/- 1.9% 5-day average) as measured by beta-galactosidase catalytic activity. NGF release from transfected DFBs was assessed over a 3-day period. Compared with control (no transfection) DFBs and DFBs transfected with vector alone, DFBs transfected with an expression vector encoding rat beta-NGF demonstrated significantly (p < 0.05) higher levels of NGF, with a 3-day maximum of 111 pg NGF per milliliter. When normalized to cell number, NGF-transfected DFBs released 1.2 pg NGF per milliliter/10(3) cells. The NGF-transfected DFBs demonstrated a maximal NGF release rate at day 1 (1.2 ng NGF/10(6) cells per day), followed by a markedly lower, sustained release rate at days 2 and 3 (0.44 ng NGF/10(6) cells per day and 0.48 ng NGF/10(6) cells per day respectively). The release rate curves for control and vector-transfected DFBs also exhibited a maximal NGF release rate at day 1, but were followed by a decreasing release rate, potentially representing in vitro degradation of NGF present in fetal bovine serum. Although not first with the development of growth factor delivery through fibroblasts, these findings suggest that rat DFBs can be modified genetically to act like Schwann's cells to deliver NGF.
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PMID:Dermal fibroblasts genetically engineered to release nerve growth factor. 1175 38


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