Differential Screening of Mutated SOD1 Transgenic Mice Reveals Early Up-Regulation of a Fast Axonal Transport Component in Spinal Cord Motor Neurons
In the present study we analyze the molecular mechanisms underlying motor neuron degeneration in familial amyotrophic lateral sclerosis (FALS). For this, we used a transgenic mouse model expressing the Cu/Zn superoxide dismutase (SOD1) gene with a Gly86 to Arg (G86R) mutation equivalent to that foun...
Main Authors: | , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2000-08-01
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Series: | Neurobiology of Disease |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996100902924 |
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doaj-72d6424233ce45a2bbfcf47b3d4487ea |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Luc Dupuis Marc de Tapia Frédérique René Bernadette Lutz-Bucher Jon W. Gordon Luc Mercken Laurent Pradier Jean-Philippe Loeffler |
spellingShingle |
Luc Dupuis Marc de Tapia Frédérique René Bernadette Lutz-Bucher Jon W. Gordon Luc Mercken Laurent Pradier Jean-Philippe Loeffler Differential Screening of Mutated SOD1 Transgenic Mice Reveals Early Up-Regulation of a Fast Axonal Transport Component in Spinal Cord Motor Neurons Neurobiology of Disease |
author_facet |
Luc Dupuis Marc de Tapia Frédérique René Bernadette Lutz-Bucher Jon W. Gordon Luc Mercken Laurent Pradier Jean-Philippe Loeffler |
author_sort |
Luc Dupuis |
title |
Differential Screening of Mutated SOD1 Transgenic Mice Reveals Early Up-Regulation of a Fast Axonal Transport Component in Spinal Cord Motor Neurons |
title_short |
Differential Screening of Mutated SOD1 Transgenic Mice Reveals Early Up-Regulation of a Fast Axonal Transport Component in Spinal Cord Motor Neurons |
title_full |
Differential Screening of Mutated SOD1 Transgenic Mice Reveals Early Up-Regulation of a Fast Axonal Transport Component in Spinal Cord Motor Neurons |
title_fullStr |
Differential Screening of Mutated SOD1 Transgenic Mice Reveals Early Up-Regulation of a Fast Axonal Transport Component in Spinal Cord Motor Neurons |
title_full_unstemmed |
Differential Screening of Mutated SOD1 Transgenic Mice Reveals Early Up-Regulation of a Fast Axonal Transport Component in Spinal Cord Motor Neurons |
title_sort |
differential screening of mutated sod1 transgenic mice reveals early up-regulation of a fast axonal transport component in spinal cord motor neurons |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2000-08-01 |
description |
In the present study we analyze the molecular mechanisms underlying motor neuron degeneration in familial amyotrophic lateral sclerosis (FALS). For this, we used a transgenic mouse model expressing the Cu/Zn superoxide dismutase (SOD1) gene with a Gly86 to Arg (G86R) mutation equivalent to that found in a subset of human FALS. Using an optimized suppression subtractive hybridization method, a cDNA specifically up-regulated during the asymptomatic phase in the lumbar spinal cord of G86R mice was identified by sequence analysis as the KIF3-associated protein (KAP3), a regulator of fast axonal transport. RT-PCR analysis revealed that KAP3 induction was an early event arising long before axonal degeneration. Immunohistochemical studies further revealed that KAP3 protein predominantly accumulates in large motor neurons of the ventral spinal cord. We further demonstrated that KAP3 up-regulation occurs independent of any change in the other components of the kinesin II complex. However, since the ubiquitous KIF1A motor is up-regulated, our results show an early and complex rearrangement of the fast axonal transport machinery in the course of FALS pathology. |
url |
http://www.sciencedirect.com/science/article/pii/S0969996100902924 |
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doaj-72d6424233ce45a2bbfcf47b3d4487ea2021-03-20T04:46:25ZengElsevierNeurobiology of Disease1095-953X2000-08-0174274285Differential Screening of Mutated SOD1 Transgenic Mice Reveals Early Up-Regulation of a Fast Axonal Transport Component in Spinal Cord Motor NeuronsLuc Dupuis0Marc de Tapia1Frédérique René2Bernadette Lutz-Bucher3Jon W. Gordon4Luc Mercken5Laurent Pradier6Jean-Philippe Loeffler7Laboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, Institut de Physiologie et Chimie Biologique, 21 Rue René Descartes, 67084, Strasbourg Cédex, France; Department of Obstetrics/Gynecology, Mount Sinaı̈ Medical Center, New York, New York, 10029; Central Nervous System Department, Aventis, Magendie Building, 13 Quai Jules Guesde, 94403, Vitry sur Seine Cédex, FranceLaboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, Institut de Physiologie et Chimie Biologique, 21 Rue René Descartes, 67084, Strasbourg Cédex, France; Department of Obstetrics/Gynecology, Mount Sinaı̈ Medical Center, New York, New York, 10029; Central Nervous System Department, Aventis, Magendie Building, 13 Quai Jules Guesde, 94403, Vitry sur Seine Cédex, FranceLaboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, Institut de Physiologie et Chimie Biologique, 21 Rue René Descartes, 67084, Strasbourg Cédex, France; Department of Obstetrics/Gynecology, Mount Sinaı̈ Medical Center, New York, New York, 10029; Central Nervous System Department, Aventis, Magendie Building, 13 Quai Jules Guesde, 94403, Vitry sur Seine Cédex, FranceLaboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, Institut de Physiologie et Chimie Biologique, 21 Rue René Descartes, 67084, Strasbourg Cédex, France; Department of Obstetrics/Gynecology, Mount Sinaı̈ Medical Center, New York, New York, 10029; Central Nervous System Department, Aventis, Magendie Building, 13 Quai Jules Guesde, 94403, Vitry sur Seine Cédex, FranceLaboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, Institut de Physiologie et Chimie Biologique, 21 Rue René Descartes, 67084, Strasbourg Cédex, France; Department of Obstetrics/Gynecology, Mount Sinaı̈ Medical Center, New York, New York, 10029; Central Nervous System Department, Aventis, Magendie Building, 13 Quai Jules Guesde, 94403, Vitry sur Seine Cédex, FranceLaboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, Institut de Physiologie et Chimie Biologique, 21 Rue René Descartes, 67084, Strasbourg Cédex, France; Department of Obstetrics/Gynecology, Mount Sinaı̈ Medical Center, New York, New York, 10029; Central Nervous System Department, Aventis, Magendie Building, 13 Quai Jules Guesde, 94403, Vitry sur Seine Cédex, FranceLaboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, Institut de Physiologie et Chimie Biologique, 21 Rue René Descartes, 67084, Strasbourg Cédex, France; Department of Obstetrics/Gynecology, Mount Sinaı̈ Medical Center, New York, New York, 10029; Central Nervous System Department, Aventis, Magendie Building, 13 Quai Jules Guesde, 94403, Vitry sur Seine Cédex, FranceLaboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, Institut de Physiologie et Chimie Biologique, 21 Rue René Descartes, 67084, Strasbourg Cédex, France; Department of Obstetrics/Gynecology, Mount Sinaı̈ Medical Center, New York, New York, 10029; Central Nervous System Department, Aventis, Magendie Building, 13 Quai Jules Guesde, 94403, Vitry sur Seine Cédex, FranceIn the present study we analyze the molecular mechanisms underlying motor neuron degeneration in familial amyotrophic lateral sclerosis (FALS). For this, we used a transgenic mouse model expressing the Cu/Zn superoxide dismutase (SOD1) gene with a Gly86 to Arg (G86R) mutation equivalent to that found in a subset of human FALS. Using an optimized suppression subtractive hybridization method, a cDNA specifically up-regulated during the asymptomatic phase in the lumbar spinal cord of G86R mice was identified by sequence analysis as the KIF3-associated protein (KAP3), a regulator of fast axonal transport. RT-PCR analysis revealed that KAP3 induction was an early event arising long before axonal degeneration. Immunohistochemical studies further revealed that KAP3 protein predominantly accumulates in large motor neurons of the ventral spinal cord. We further demonstrated that KAP3 up-regulation occurs independent of any change in the other components of the kinesin II complex. However, since the ubiquitous KIF1A motor is up-regulated, our results show an early and complex rearrangement of the fast axonal transport machinery in the course of FALS pathology.http://www.sciencedirect.com/science/article/pii/S0969996100902924 |