The tyrosinase related protein-1 (Tyrp1) promoter in transgenic experiments: targeted expression to the retinal pigment epithelium.
Transgenic experiments targeting gene expression to the retinal pigment epithelium (RPE) require use of a pigment cell-specific promoter. We have chosen 1.4 kb and 4 kb from the promoter of the tyrosinase-related protein 1 gene (Tyrp1) for RPE-specific expression, since Tyrp1 mRNA and protein are detected already at midgestation in this epithelial layer. In eyes of transgenic embryos, expression of the Tyrp1-lacZ fusion construct led to strong and specific expression of beta-galactosidase in the RPE from day E10.5 onwards. The promoter thus proved useful to target expression of two different oncogenes to the RPE, a constitutively active tyrosine kinase receptor (Rfp/Ret) and SV40 T antigen (Tag). Tyrp1-Rfp/Ret transgenic mice developed microphthalmia, primarily induced by changes in the developing RPE. In addition, Tyrp1-Rfp/Ret expression induced proliferation of RPE cells leading to benign RPE tumors in the adult. Tyrp1-Tag transgenic mice developed malignant eye tumors of RPE origin, which invaded the optic nerve and led to metastasis into lymph nodes and spleen.
Beermann
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F
ISREC (Swiss Institute for Experimental Cancer Research), Epalinges. Friedrich.Beerman@isrec.unil.ch
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005134:Eye Neoplasms / Q000235:genetics / Q000473:pathology; D005326:Fetal Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007763:Lac Operon; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008850:Microphthalmos / Q000235:genetics; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000633:toxicity; D009857:Oncogenes; D010088:Oxidoreductases; D010857:Pigment Epithelium of Eye / Q000196:embryology / Q000378:metabolism*; D010858:Pigmentation / Q000235:genetics; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000633:toxicity; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D000070584:Tripartite Motif Proteins
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005326:Fetal Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D010088:Oxidoreductases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D044767:Ubiquitin-Protein Ligases; C489799:TYRP1 protein, human; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; C489296:Trim27 protein, mouse; D000070584:Tripartite Motif Proteins; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse