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Publication : TRAIL-related death receptors in normal, Lurcher and weaver mutant mouse brain.

First Author  Bäurle J Year  2004
Journal  Neurosci Lett Volume  372
Issue  1-2 Pages  46-51
PubMed ID  15531086 Mgi Jnum  J:107527
Mgi Id  MGI:3621379 Doi  10.1016/j.neulet.2004.09.009
Citation  Baurle J, et al. (2004) TRAIL-related death receptors in normal, Lurcher and weaver mutant mouse brain. Neurosci Lett 372(1-2):46-51
abstractText  In this study, we searched for murine analogues of the four death-receptor types (TRAIL-R1 to R4), targeted by the tumour necrosis factor related apoptosis inducing ligand (TRAIL), which were recently identified in the human brain. The expression of TRAIL-receptors in the normal murine brain was investigated using antibodies directed against different epitopes of the human TRAIL-receptors. Mouse mutants, in particular weaver and Lurcher with their well defined spatio-temporal patterns of neurodegeneration in the cerebellum, the inferior olive and the substantia nigra, were used as a model for investigating a potential contribution of TRAIL-receptors to the genetically determined cell death observed in these mutants. Although all antibodies used, recognized the respective human antigens, only the murine analogue of the human TRAIL-R2 epitope was also identified in the mouse brain. Antisera against human TRAIL-R1, TRAIL-R3 and TRAIL-R4 failed to reveal any other murine TRAIL-receptor analogue. In normal mice, TRAIL-R2 is not universally expressed throughout the brain but rather restricted to specific neuronal populations predominantly consisting of large neurons. In weaver, the spatial patterns and relative densities of TRAIL-R2 labelling were virtually identical to those seen in wild-types during the period of cell death in the cerebellum and the substantia nigra. In Lurcher, TRAIL-R2 expression in cerebellar granule cells and inferior olivary neurons was identical to that in wildtypes but significantly reduced in Purkinje cells undergoing degeneration. Thus, although TRAIL-R2 is found to be expressed in various cell types of the murine brain, cell death in weaver and Lurcher mutants is apparently not accompanied by an upregulation of TRAIL-receptors.
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