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Updated: Aug 13, 2026
Mouse Models of Periventricular Leukomalacia
Published on: May 19, 2010
TRAIL-related death receptors in normal, Lurcher and weaver mutant mouse brain
Jörg Bäurle1, Sabine Frischmuth, Karel Kranda
1Department of Physiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, D-14195 Berlin, Germany. baeurle@zedat.fu-berlin.de
Abstract:
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.
Insights
Researchers identified a murine analogue for only one of four human TRAIL-receptors (TRAIL-R2) in the mouse brain. This TRAIL-R2 expression did not increase during neurodegeneration in specific mouse mutants.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) targets four death-receptor types (TRAIL-R1 to R4).
- TRAIL-receptors have been identified in the human brain, suggesting a role in neuronal function or pathology.
- Understanding TRAIL-receptor expression in the mouse brain is crucial for modeling human neurological conditions.
Purpose of the Study:
- To identify murine analogues of human TRAIL-receptors (TRAIL-R1 to R4).
- To investigate the expression patterns of TRAIL-receptors in the normal murine brain.
- To examine the potential role of TRAIL-receptors in genetically determined neurodegeneration using weaver and Lurcher mouse mutants.
Main Methods:
- Utilized antibodies against human TRAIL-receptors to detect their murine counterparts.
- Examined TRAIL-receptor expression in normal mice and in weaver and Lurcher neurodegenerative models.
- Analyzed spatio-temporal patterns of TRAIL-R2 expression in relation to cell death in specific brain regions.
Main Results:
- Only a murine analogue of human TRAIL-R2 was identified in the mouse brain; TRAIL-R1, TRAIL-R3, and TRAIL-R4 analogues were not detected.
- TRAIL-R2 expression in normal mice was restricted to specific neuronal populations, primarily large neurons.
- In weaver and Lurcher mutants, TRAIL-R2 expression patterns were largely similar to wild-types, with no observed upregulation during neurodegeneration, except for a reduction in Purkinje cells in Lurcher mutants.
Conclusions:
- Murine TRAIL-R2 is expressed in specific neuronal populations within the brain.
- The identified TRAIL-R2 is not upregulated during the neurodegenerative processes in weaver and Lurcher mouse models.
- These findings suggest that TRAIL-R2 may not play a significant role in the genetically determined cell death observed in these specific murine mutants.
