Abstract
The 37-kDa/67-kDa laminin receptor (LRP/LR) plays a major role in the propagation of PrPSc, the abnormal form of the prion protein. In order to ablate the expression of LRP/LR in mouse brain we generated transgenic mice ectopically expressing antisense LRP RNA in the brain under control of the neuron-specific enolase (NSE) promoter. Hemizygous transgenic mice TgN(NSEasLRP)2 showed a significant reduction of LRP/LR protein levels in hippocampal and cerebellar brain regions. These mice might act as powerful tools to investigate the role of the laminin receptor in scrapie pathogenesis.
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References
Forss Petter S, Danielson PE, Catsicas S, Battenberg E, Price J, Nerenberg M et al. (1990) Transgenic mice expressing betagalactosidase in mature neurons under neuron-specific enolase promoter control. Neuron 5: 187–197.
Fraser H and Dickinson AG (1967) Distribution of experimentally induced scrapie lesions in the brain. Nature 216: 1310–1311.
Gauczynski S, Hundt C, Leucht C and Weiss S (2001a) Interaction of prion proteins with cell surface receptors, molecular chaperones, and other molecules. Adv Protein Chem 57: 229–272.
Gauczynski S et al. (2001b) The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. EMBO J 20: 5863–5875.
Hundt C et al. (2001) Identification of interaction domains of the prion protein with its 37-kDa/67-kDa laminin receptor. EMBO J 20: 5876–5886.
Lasmézas CI, Deslys JP, Demaimay R, Adjou KT, Hauw JJ and Dormont D (1996) Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy. J Gen Virol 77: 1601–1609.
Lasmézas CI and Weiss S (2000) Molecular biology of prion diseases. In: Cary JW, Linz JE and Bhatnagar D (eds),Microbial Foodborne Diseases. Mechanisms of Pathogenicity and Toxin Synthesis. (pp. 495–537) Technomic Publishing Co., Inc., Lancaster USA.
Leucht C and Weiss S (2002) Der Prion-Protein-Rezeptor.In: Brem M and Müller M (eds), BSE-Wahnsinn und Wirklichkeit. Vol. 87 (pp. 39–54) Nova Acta Leopoldina, Halle.
Leucht C, Simoneau S, Rey C, Vana K, Rieger R, Lasmézas CI et al. (2003) The 37-kDa/67-kDa laminin receptor is required for PrPSc propagation in scrapie-infected neuronal cells. EMBO Rep 4: 290–295.
McKinley MP, Meyer RK, Kenaga L, Rahbar F, Cotter R, Serban A et al. (1991) Scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis. J Virol 65: 1340–1351.
Pepin MC, Pothier F and Barden N (1992) Impaired type II glucocorticoid-receptor function in mice bearing antisense RNA transgene. Nature 355: 725–728.
Prusiner SB (1998) Prions. Proc Natl Acad Sci USA 95: 13363–13383.
Rieger R, Edenhofer F, Lasmezas CI and Weiss S (1997) The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cells. Nat Med 3: 1383–1388.
Simoneau S, Haïk S, Leucht C, Dormont D, Deslys J-P, Weiss S et al. (2003) Different isoforms of the non-integrin laminin receptor are present in mouse brain and bind PrP. Biol Chem 384: 243–246.
Weissmann C and Aguzzi A (1997) Bovine spongiform encephalopathy and early onset variant Creutzfeldt-Jakob disease. Curr Opin Neurobiol 7: 695–700.
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Leucht, C., Vana, K., Renner-Müller, I. et al. Knock-Down of the 37-kDa/67-kDa Laminin Receptor in Mouse Brain by Transgenic Expression of Specific Antisense LRP RNA. Transgenic Res 13, 81–85 (2004). https://doi.org/10.1023/B:TRAG.0000017177.35197.89
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DOI: https://doi.org/10.1023/B:TRAG.0000017177.35197.89