Expression of X-chromosome linked inhibitor of apoptosis protein in mature purkinje cells and in retinal bipolar cells in transgenic mice induces neurodegeneration

L Korhonen, I Hansson, C Maugras, R Wehrle, M Kairisalo, A Borgkvist, Eija Jokitalo, C Sotelo, G Fisone, I Dusart, D Lindholm

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Transgenic mice with overexpression of the caspase-inhibitor, X-chromosome-linked inhibitor of apoptosis protein (XIAP) in Purkinje cell (PC) and in retinal bipolar cells (RBCs) were produced to study the regulation of cell death. Unexpectedly, an increased neurodegeneration was observed in the PCs in these L7-XIAP mice after the third postnatal week with the mice exhibiting severe ataxia. The loss of PCs was independent of Bax as shown by crossing the L7-XIAP mice with Bax gene-deleted mice. Electron microscopy revealed intact organelles in PCs but with the stacking of ER cisterns indicative of cell stress. Immunostaining for cell death proteins showed an increased phosphorylation of c-Jun in the PCs, suggesting an involvement in cell degeneration. Apart from PCs, the number of RBCs was decreased in adult retina in line with the expression pattern for the L7 promoter. The data show that overexpression of the anti-apoptotic protein XIAP in vulnerable neurons leads to enhanced cell death. The mechanisms underlying this neurodegeneration can be related to the effects of XIAP on cell stress and altered cell signaling. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
Original languageEnglish
JournalNeuroscience
Volume156
Issue number3
Pages (from-to)515-526
Number of pages12
ISSN0306-4522
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 311 Basic medicine
  • 118 Biological sciences
  • 515 Psychology

Cite this

Korhonen, L ; Hansson, I ; Maugras, C ; Wehrle, R ; Kairisalo, M ; Borgkvist, A ; Jokitalo, Eija ; Sotelo, C ; Fisone, G ; Dusart, I ; Lindholm, D. / Expression of X-chromosome linked inhibitor of apoptosis protein in mature purkinje cells and in retinal bipolar cells in transgenic mice induces neurodegeneration. In: Neuroscience. 2008 ; Vol. 156, No. 3. pp. 515-526.
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title = "Expression of X-chromosome linked inhibitor of apoptosis protein in mature purkinje cells and in retinal bipolar cells in transgenic mice induces neurodegeneration",
abstract = "Transgenic mice with overexpression of the caspase-inhibitor, X-chromosome-linked inhibitor of apoptosis protein (XIAP) in Purkinje cell (PC) and in retinal bipolar cells (RBCs) were produced to study the regulation of cell death. Unexpectedly, an increased neurodegeneration was observed in the PCs in these L7-XIAP mice after the third postnatal week with the mice exhibiting severe ataxia. The loss of PCs was independent of Bax as shown by crossing the L7-XIAP mice with Bax gene-deleted mice. Electron microscopy revealed intact organelles in PCs but with the stacking of ER cisterns indicative of cell stress. Immunostaining for cell death proteins showed an increased phosphorylation of c-Jun in the PCs, suggesting an involvement in cell degeneration. Apart from PCs, the number of RBCs was decreased in adult retina in line with the expression pattern for the L7 promoter. The data show that overexpression of the anti-apoptotic protein XIAP in vulnerable neurons leads to enhanced cell death. The mechanisms underlying this neurodegeneration can be related to the effects of XIAP on cell stress and altered cell signaling. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.",
keywords = "311 Basic medicine, 118 Biological sciences, 515 Psychology",
author = "L Korhonen and I Hansson and C Maugras and R Wehrle and M Kairisalo and A Borgkvist and Eija Jokitalo and C Sotelo and G Fisone and I Dusart and D Lindholm",
year = "2008",
doi = "10.1016/j.neuroscience.2008.08.005",
language = "English",
volume = "156",
pages = "515--526",
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Korhonen, L, Hansson, I, Maugras, C, Wehrle, R, Kairisalo, M, Borgkvist, A, Jokitalo, E, Sotelo, C, Fisone, G, Dusart, I & Lindholm, D 2008, 'Expression of X-chromosome linked inhibitor of apoptosis protein in mature purkinje cells and in retinal bipolar cells in transgenic mice induces neurodegeneration' Neuroscience, vol. 156, no. 3, pp. 515-526. https://doi.org/10.1016/j.neuroscience.2008.08.005

Expression of X-chromosome linked inhibitor of apoptosis protein in mature purkinje cells and in retinal bipolar cells in transgenic mice induces neurodegeneration. / Korhonen, L; Hansson, I; Maugras, C; Wehrle, R; Kairisalo, M; Borgkvist, A; Jokitalo, Eija; Sotelo, C; Fisone, G; Dusart, I; Lindholm, D.

In: Neuroscience, Vol. 156, No. 3, 2008, p. 515-526.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Expression of X-chromosome linked inhibitor of apoptosis protein in mature purkinje cells and in retinal bipolar cells in transgenic mice induces neurodegeneration

AU - Korhonen, L

AU - Hansson, I

AU - Maugras, C

AU - Wehrle, R

AU - Kairisalo, M

AU - Borgkvist, A

AU - Jokitalo, Eija

AU - Sotelo, C

AU - Fisone, G

AU - Dusart, I

AU - Lindholm, D

PY - 2008

Y1 - 2008

N2 - Transgenic mice with overexpression of the caspase-inhibitor, X-chromosome-linked inhibitor of apoptosis protein (XIAP) in Purkinje cell (PC) and in retinal bipolar cells (RBCs) were produced to study the regulation of cell death. Unexpectedly, an increased neurodegeneration was observed in the PCs in these L7-XIAP mice after the third postnatal week with the mice exhibiting severe ataxia. The loss of PCs was independent of Bax as shown by crossing the L7-XIAP mice with Bax gene-deleted mice. Electron microscopy revealed intact organelles in PCs but with the stacking of ER cisterns indicative of cell stress. Immunostaining for cell death proteins showed an increased phosphorylation of c-Jun in the PCs, suggesting an involvement in cell degeneration. Apart from PCs, the number of RBCs was decreased in adult retina in line with the expression pattern for the L7 promoter. The data show that overexpression of the anti-apoptotic protein XIAP in vulnerable neurons leads to enhanced cell death. The mechanisms underlying this neurodegeneration can be related to the effects of XIAP on cell stress and altered cell signaling. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

AB - Transgenic mice with overexpression of the caspase-inhibitor, X-chromosome-linked inhibitor of apoptosis protein (XIAP) in Purkinje cell (PC) and in retinal bipolar cells (RBCs) were produced to study the regulation of cell death. Unexpectedly, an increased neurodegeneration was observed in the PCs in these L7-XIAP mice after the third postnatal week with the mice exhibiting severe ataxia. The loss of PCs was independent of Bax as shown by crossing the L7-XIAP mice with Bax gene-deleted mice. Electron microscopy revealed intact organelles in PCs but with the stacking of ER cisterns indicative of cell stress. Immunostaining for cell death proteins showed an increased phosphorylation of c-Jun in the PCs, suggesting an involvement in cell degeneration. Apart from PCs, the number of RBCs was decreased in adult retina in line with the expression pattern for the L7 promoter. The data show that overexpression of the anti-apoptotic protein XIAP in vulnerable neurons leads to enhanced cell death. The mechanisms underlying this neurodegeneration can be related to the effects of XIAP on cell stress and altered cell signaling. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

KW - 311 Basic medicine

KW - 118 Biological sciences

KW - 515 Psychology

U2 - 10.1016/j.neuroscience.2008.08.005

DO - 10.1016/j.neuroscience.2008.08.005

M3 - Article

VL - 156

SP - 515

EP - 526

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 3

ER -