A Mutant ataxin-3 fragment results from processing at a site N-terminal to amino acid 190 in brain of Machado-Joseph disease-like transgenic mice

Veronica F. Colomer Gould, Daniel Goti, Donna Pearce, Guillermo A. Gonzalez, Hong Gao, Mario Bermudez de Leon, Nancy A. Jenkins, Neal G. Copeland, Christopher A. Ross, Dale R. Brown

Resultado de la investigación

41 Citas (Scopus)

Resumen

Machado-Joseph disease also called spinocerebellar ataxia type 3 (MJD/SCA3) is a hereditary and neurodegenerative movement disorder caused by ataxin-3 with a polyglutamine expansion (mutant ataxin-3). Neuronal loss in MJD/SCA3 is associated with a mutant ataxin-3 toxic fragment. Defining mutant ataxin-3 proteolytic site(s) could facilitate the identification of the corresponding enzyme(s). Previously, we reported a mutant ataxin-3 mjd1a fragment in the brain of transgenic mice (Q71) that contained epitopes C-terminal to amino acid 220. In this study, we generated and characterized neuroblastoma cells and transgenic mice expressing mutant ataxin-3 mjd1a lacking amino acids 190-220 (deltaQ71). Less deltaQ71 than Q71 fragments were detected in the cell but not mouse model. The transgenic mice developed an MJD/SCA3-like phenotype and their brain homogenates had a fragment containing epitopes C-terminal to amino acid 220. Our results support the toxic fragment hypothesis and narrow the mutant ataxin-3 cleavage site to the N-terminus of amino acid 190. © 2007 Elsevier Inc. All rights reserved.
Idioma originalEnglish
Páginas (desde-hasta)362-369
Número de páginas8
PublicaciónNeurobiology of Disease
DOI
EstadoPublished - 1 sep 2007
Publicado de forma externa

Huella dactilar

Machado-Joseph Disease
Transgenic Mice
Amino Acids
Brain
Poisons
Epitopes
Movement Disorders
Ataxin-3
Neuroblastoma
Neurodegenerative Diseases
Phenotype
Enzymes

All Science Journal Classification (ASJC) codes

  • Neurology

Citar esto

Colomer Gould, Veronica F. ; Goti, Daniel ; Pearce, Donna ; Gonzalez, Guillermo A. ; Gao, Hong ; Bermudez de Leon, Mario ; Jenkins, Nancy A. ; Copeland, Neal G. ; Ross, Christopher A. ; Brown, Dale R. / A Mutant ataxin-3 fragment results from processing at a site N-terminal to amino acid 190 in brain of Machado-Joseph disease-like transgenic mice. En: Neurobiology of Disease. 2007 ; pp. 362-369.
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title = "A Mutant ataxin-3 fragment results from processing at a site N-terminal to amino acid 190 in brain of Machado-Joseph disease-like transgenic mice",
abstract = "Machado-Joseph disease also called spinocerebellar ataxia type 3 (MJD/SCA3) is a hereditary and neurodegenerative movement disorder caused by ataxin-3 with a polyglutamine expansion (mutant ataxin-3). Neuronal loss in MJD/SCA3 is associated with a mutant ataxin-3 toxic fragment. Defining mutant ataxin-3 proteolytic site(s) could facilitate the identification of the corresponding enzyme(s). Previously, we reported a mutant ataxin-3 mjd1a fragment in the brain of transgenic mice (Q71) that contained epitopes C-terminal to amino acid 220. In this study, we generated and characterized neuroblastoma cells and transgenic mice expressing mutant ataxin-3 mjd1a lacking amino acids 190-220 (deltaQ71). Less deltaQ71 than Q71 fragments were detected in the cell but not mouse model. The transgenic mice developed an MJD/SCA3-like phenotype and their brain homogenates had a fragment containing epitopes C-terminal to amino acid 220. Our results support the toxic fragment hypothesis and narrow the mutant ataxin-3 cleavage site to the N-terminus of amino acid 190. {\circledC} 2007 Elsevier Inc. All rights reserved.",
author = "{Colomer Gould}, {Veronica F.} and Daniel Goti and Donna Pearce and Gonzalez, {Guillermo A.} and Hong Gao and {Bermudez de Leon}, Mario and Jenkins, {Nancy A.} and Copeland, {Neal G.} and Ross, {Christopher A.} and Brown, {Dale R.}",
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A Mutant ataxin-3 fragment results from processing at a site N-terminal to amino acid 190 in brain of Machado-Joseph disease-like transgenic mice. / Colomer Gould, Veronica F.; Goti, Daniel; Pearce, Donna; Gonzalez, Guillermo A.; Gao, Hong; Bermudez de Leon, Mario; Jenkins, Nancy A.; Copeland, Neal G.; Ross, Christopher A.; Brown, Dale R.

En: Neurobiology of Disease, 01.09.2007, p. 362-369.

Resultado de la investigación

TY - JOUR

T1 - A Mutant ataxin-3 fragment results from processing at a site N-terminal to amino acid 190 in brain of Machado-Joseph disease-like transgenic mice

AU - Colomer Gould, Veronica F.

AU - Goti, Daniel

AU - Pearce, Donna

AU - Gonzalez, Guillermo A.

AU - Gao, Hong

AU - Bermudez de Leon, Mario

AU - Jenkins, Nancy A.

AU - Copeland, Neal G.

AU - Ross, Christopher A.

AU - Brown, Dale R.

PY - 2007/9/1

Y1 - 2007/9/1

N2 - Machado-Joseph disease also called spinocerebellar ataxia type 3 (MJD/SCA3) is a hereditary and neurodegenerative movement disorder caused by ataxin-3 with a polyglutamine expansion (mutant ataxin-3). Neuronal loss in MJD/SCA3 is associated with a mutant ataxin-3 toxic fragment. Defining mutant ataxin-3 proteolytic site(s) could facilitate the identification of the corresponding enzyme(s). Previously, we reported a mutant ataxin-3 mjd1a fragment in the brain of transgenic mice (Q71) that contained epitopes C-terminal to amino acid 220. In this study, we generated and characterized neuroblastoma cells and transgenic mice expressing mutant ataxin-3 mjd1a lacking amino acids 190-220 (deltaQ71). Less deltaQ71 than Q71 fragments were detected in the cell but not mouse model. The transgenic mice developed an MJD/SCA3-like phenotype and their brain homogenates had a fragment containing epitopes C-terminal to amino acid 220. Our results support the toxic fragment hypothesis and narrow the mutant ataxin-3 cleavage site to the N-terminus of amino acid 190. © 2007 Elsevier Inc. All rights reserved.

AB - Machado-Joseph disease also called spinocerebellar ataxia type 3 (MJD/SCA3) is a hereditary and neurodegenerative movement disorder caused by ataxin-3 with a polyglutamine expansion (mutant ataxin-3). Neuronal loss in MJD/SCA3 is associated with a mutant ataxin-3 toxic fragment. Defining mutant ataxin-3 proteolytic site(s) could facilitate the identification of the corresponding enzyme(s). Previously, we reported a mutant ataxin-3 mjd1a fragment in the brain of transgenic mice (Q71) that contained epitopes C-terminal to amino acid 220. In this study, we generated and characterized neuroblastoma cells and transgenic mice expressing mutant ataxin-3 mjd1a lacking amino acids 190-220 (deltaQ71). Less deltaQ71 than Q71 fragments were detected in the cell but not mouse model. The transgenic mice developed an MJD/SCA3-like phenotype and their brain homogenates had a fragment containing epitopes C-terminal to amino acid 220. Our results support the toxic fragment hypothesis and narrow the mutant ataxin-3 cleavage site to the N-terminus of amino acid 190. © 2007 Elsevier Inc. All rights reserved.

U2 - 10.1016/j.nbd.2007.06.005

DO - 10.1016/j.nbd.2007.06.005

M3 - Article

SP - 362

EP - 369

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

ER -