Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A distal upstream regulatory element of the mouse tyrosinase gene has locus control region (LCR)-like activity and is required for position-independent expression of linked genes. It consists of a DNAse I hypersensitive site, which has enhancer activity in neural crest-derived melanocytes, embedded within a scaffold/matrix attachment region (S/MAR), both of which are necessary for LCR activity. To address the role of the S/MAR in position-independent expression, we assessed the ability of a fragment containing most of the S/MAR to insulate a transgene from position effects. The S/MAR sequence showed a striking cell type specificity in its function in all six multicopy transgenic lines, dampening position effects considerably in cutaneous melanocytes while allowing no expression in other neural crest-derived melanocytes, and causing elevated expression in ocular melanocytes derived from the neural tube. The specificity of transgene expression in the eye suggested the presence of both positive and negative regulatory elements in this enhancer/S/MAR region, which was confirmed by transient transfection analyses. This is the first known regulatory element to exhibit different activities in melanocytes of different developmental origins.
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PMID:Distal upstream tyrosinase S/MAR-containing sequence has regulatory properties specific to subsets of melanocytes. 1040 71

At has been reported that transplantation of appropriate cells, growth factors, and/or extracellular matrix may help the regeneration of damaged tissues or organs. Some growth factors, such as basic fibroblast growth factor(bFGF), have been successfully transferred to patients with ischemic heart disease. Embryonic dopamine neurons were also transplanted into the brains of patients with Parkinson's disease successfully. We have also performed cultured auto iris pigment epithelial cell (IPE) transplantation into the subretinal space after removal of choroidal neovascularization in patients with age-related macular degeneration (AMD). Here, we report the results of auto IPE transplantation in 35 patients, who could be followed for more than 6 months. We also tried to apply cell transplantation to other retinal diseases by managing the transplanted cells as introduced growth factor genes. Auto IPE transplantation was performed after removal of choroidal neovascular membranes (CNV). Visual acuity wes improved by more than 0.2 log MAR in 18 of 35 patients (51.5%), it was unchanged in 11 patients (31.5%), and it was worsened in 6 patients (17%). No significant difference was observed in comparison to patients who underwent CNV removal only. However, unlike the previous reports, we found no patients showing rejection. We also found that the cultured transplanted cells never showed proliferation under the retina or in the vitreous cavity and concluded that cultured auto IPE transplantation can be performed safely without complications. Next, we examined whether cell transplantation can be expanded to other degenerative retinal diseases. One of our results showed that host RPE may play an important role against the transplanted cells in the subretinal regions. When we introduced bFGF gene into the cells, we found synexpression cluster of the genes in the cells. One of the most prominent movements among the genes was lysyl oxidase like-1 gene, which plays an important role in the maturation of the extracellular collagen and in cell attachment. However, when we examined the cell attachment on the culture plates after 12 hours of culture, no significant difference was observed between the cells with or without bFGF. Further, when we examined the area of the cells transplanted into the subretinal space of rats during successive follow-up using fluorescein marker (EGFP), no statistical significance was observed. The gene expression pattern may be different when we introduce different growth factor gene. No antibody production was generated against the growth factor gene introduced cells after cell transplantation. Further, when we made transgenic mice expressing bFGF or Axokine cDNA in the RPE of rd mice, no photoreceptor degeneration was observed. One of the reasons was suspected to be that bFGF was expressed systemically by the promoter of tyrosinase related-protein 1 gene and may lead to lethality. Another reason was suspected to be suppression of the function of Axokine by the down-regulation of the ciliary neurotrophic factor or its receptor gene. Conversely, when we produced photoreceptor degeneration by constant light damage in the rats, we found partial photoreceptor rescue by transplantation of the growth factor gene introduced RPE. We show here the possibility that growth factor gene introduced cell transplantation may be applied to retinal diseases, if we select appropriate cells and genes.
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PMID:[Regeneration of the retina using pigment epithelial cell transplantation]. 1261 Aug 37