Studies on neuronal death in the mouse model of Niemann-Pick C disease
- Author(s)
- Erickson, RP; Bernard, O;
- Details
- Publication Year 2002-06-15,Volume 68,Issue #6,Page 738-744
- Journal Title
- JOURNAL OF NEUROSCIENCE RESEARCH
- Publication Type
- Journal Article
- Abstract
- A mouse model of Niemann-Pick disease type C (NPC) carries a genetic defect that causes biochemical changes in lipid levels and a progressive neuropathology that parallels the effects of NPC disease in humans. It is a moot point whether or not the loss of Purkinje and other neuronal cells proceeds by apoptotic death. Therefore, we have introduced into these mice a transgene expressing human Bcl-2 protein which has previously been demonstrated to prevent developmental neuronal death and death induced by a variety of stimuli. The human Bcl-2 transgene was driven by the neuron-specific enolase promoter and was abundantly expressed in Purkinje and other neuronal cells. npcl(-/-)/bcl-2 transgenic mice did not show a significant delay in the onset of neurological disorders. Neuropathological examination of the npc1(-/-)/bcl-2 transgenic mice did not disclose significant differences in numbers of surviving Purkinje cells between the npc1(-/-), tg(+) and np1(-/-), tg(-) mice. When the npc1(-/-) mice were treated with minocycline, a drug which was shown to inhibit apparent apoptotic death in other mouse models of neurological disease, no delay in onset of neurological disorders were observed in either npc1(-/-) or npc1(-/-)/mdrla(-/-) mice (mdr1a deficiency was used to enhance brain availability of minocycline). Caspase-1 levels were not altered in npc1(-/-) mice, with or without minocycline treatment. These results suggest that Purkinje cell loss in npcl(-/-) mice does not proceed by an apoptotic pathway that can be inhibited by Bcl-2 or minocycline. (C) 2002 Wiley-Liss, Inc.
- Publisher
- WILEY-LISS
- Keywords
- INDUCED CELL-DEATH; TRANSGENIC MICE; P-GLYCOPROTEIN; CHOLESTEROL HOMEOSTASIS; BCL-2 TRANSGENE; GENE-EXPRESSION; MURINE MODEL; SURVIVAL; CERAMIDE; SPHINGOSINE
- Publisher's Version
- https://doi.org/10.1002/jnr.10257
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-06-15 12:00:00