共 74 条
YAC transgenic mice carrying pathological alleles of the MJD1 locus exhibit a mild and slowly progressive cerebellar deficit
被引:150
作者:

Cemal, CK
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England

Carroll, CJ
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England

Lawrence, L
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England

Lowrie, MB
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England

Ruddle, P
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England

Al-Mahdawi, S
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England

King, RHM
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England

Pook, MA
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England

Huxley, C
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England

Chamberlain, S
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England
机构:
[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England
[2] UCL Royal Free & Univ Coll Med Sch, London NW3 2PF, England
关键词:
D O I:
10.1093/hmg/11.9.1075
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Machado-Joseph disease (MJD; MIM 109150) is a late-onset neurodegenerative disorder caused by the expansion of a polyglutamine tract within the MJD1 gene. We have previously reported the generation of human yeast artificial chromosome (YAC) constructs encompassing the MJD1 locus into which expanded (CAG)(76) and (CAG)(84) repeat motifs have been introduced by homologous recombination. Transgenic mice containing pathological alleles with polyglutamine tract lengths of 64, 67, 72, 76 and 84 repeats, as well as the wild type with 15 repeats, have now been generated using these YAC constructs. The mice with expanded alleles demonstrate a mild and slowly progressive cerebellar deficit, manifesting as early as 4 weeks of age. As the disease progresses, pelvic elevation becomes markedly flattened, accompanied by hypotonia, and motor and sensory loss. Neuronal intranuclear inclusion (NII) formation and cell loss is prominent in the pontine and dentate nuclei, with variable cell loss in other regions of the cerebellum from 4 weeks of age. Interestingly, peripheral nerve demyelination and axonal loss is detected in symptomatic mice from 26 weeks of age. In contrast, transgenic mice carrying the wild-type (CAG)15 allele of the MJD1 locus appear completely normal at 20 months. Disease severity increases with the level of expression of the expanded protein and the size of the repeat. These mice are representative of MJD and will be a valuable resource for the detailed analysis of the roles of repeat length, tissue specificity and level of expression in the neurodegenerative processes underlying MJD pathogenesis.
引用
收藏
页码:1075 / 1094
页数:20
相关论文
共 74 条
[61]
Nuclear accumulation of truncated atrophin-1 fragments in a transgenic mouse model of DRPLA
[J].
Schilling, G
;
Wood, JD
;
Kui, DA
;
Slunt, HH
;
Gonzales, V
;
Yamada, M
;
Cooper, JK
;
Margolis, RL
;
Jenkins, NA
;
Copeland, NG
;
Takahashi, H
;
Tsuji, S
;
Price, DL
;
Borchelt, DR
;
Ross, CA
.
NEURON,
1999, 24 (01)
:275-286

Schilling, G
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Wood, JD
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Kui, DA
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Slunt, HH
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Gonzales, V
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Yamada, M
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Cooper, JK
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Margolis, RL
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Jenkins, NA
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Copeland, NG
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Takahashi, H
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Tsuji, S
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Price, DL
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Borchelt, DR
论文数: 0 引用数: 0
h-index: 0
机构:
Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

Ross, CA
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[62]
Characterization of the rat spinocerebellar ataxia type 3 gene
[J].
Schmitt, I
;
Brattig, T
;
Gossen, M
;
Riess, O
.
NEUROGENETICS,
1997, 1 (02)
:103-112

Schmitt, I
论文数: 0 引用数: 0
h-index: 0
机构:
Ruhr Univ Bochum, D-44780 Bochum, Germany Ruhr Univ Bochum, D-44780 Bochum, Germany

Brattig, T
论文数: 0 引用数: 0
h-index: 0
机构:
Ruhr Univ Bochum, D-44780 Bochum, Germany Ruhr Univ Bochum, D-44780 Bochum, Germany

Gossen, M
论文数: 0 引用数: 0
h-index: 0
机构:
Ruhr Univ Bochum, D-44780 Bochum, Germany Ruhr Univ Bochum, D-44780 Bochum, Germany

Riess, O
论文数: 0 引用数: 0
h-index: 0
机构:
Ruhr Univ Bochum, D-44780 Bochum, Germany Ruhr Univ Bochum, D-44780 Bochum, Germany
[63]
CYCLIN D1 PROVIDES A LINK BETWEEN DEVELOPMENT AND ONCOGENESIS IN THE RETINA AND BREAST
[J].
SICINSKI, P
;
DONAHER, JL
;
PARKER, SB
;
LI, TS
;
GARDNER, H
;
HASLAM, SZ
;
BRONSON, RT
;
ELLEDGE, SJ
;
WEINBERG, RA
.
CELL,
1995, 82 (04)
:621-630

SICINSKI, P
论文数: 0 引用数: 0
h-index: 0
机构: MIT,DEPT BIOL,CAMBRIDGE,MA 02142

DONAHER, JL
论文数: 0 引用数: 0
h-index: 0
机构: MIT,DEPT BIOL,CAMBRIDGE,MA 02142

PARKER, SB
论文数: 0 引用数: 0
h-index: 0
机构: MIT,DEPT BIOL,CAMBRIDGE,MA 02142

LI, TS
论文数: 0 引用数: 0
h-index: 0
机构: MIT,DEPT BIOL,CAMBRIDGE,MA 02142

GARDNER, H
论文数: 0 引用数: 0
h-index: 0
机构: MIT,DEPT BIOL,CAMBRIDGE,MA 02142

HASLAM, SZ
论文数: 0 引用数: 0
h-index: 0
机构: MIT,DEPT BIOL,CAMBRIDGE,MA 02142

BRONSON, RT
论文数: 0 引用数: 0
h-index: 0
机构: MIT,DEPT BIOL,CAMBRIDGE,MA 02142

ELLEDGE, SJ
论文数: 0 引用数: 0
h-index: 0
机构: MIT,DEPT BIOL,CAMBRIDGE,MA 02142

WEINBERG, RA
论文数: 0 引用数: 0
h-index: 0
机构: MIT,DEPT BIOL,CAMBRIDGE,MA 02142
[64]
Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures
[J].
Skinner, PJ
;
Koshy, BT
;
Cummings, CJ
;
Klement, IA
;
Helin, K
;
Servadio, A
;
Zoghbi, HY
;
Orr, HT
.
NATURE,
1997, 389 (6654)
:971-974

Skinner, PJ
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MINNESOTA, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA

Koshy, BT
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MINNESOTA, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA

Cummings, CJ
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MINNESOTA, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA

Klement, IA
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MINNESOTA, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA

Helin, K
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MINNESOTA, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA

Servadio, A
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MINNESOTA, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA

Zoghbi, HY
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MINNESOTA, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA

Orr, HT
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MINNESOTA, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA
[65]
Homozygosity for Machado-Joseph disease gene enhances phenotypic severity
[J].
Sobue, G
;
Doyu, M
;
Nakao, N
;
Shimada, N
;
Mitsuma, T
;
Maruyama, H
;
Kawakami, H
;
Nakamura, S
.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY,
1996, 60 (03)
:354-356

Sobue, G
论文数: 0 引用数: 0
h-index: 0
机构: AICHI MED UNIV,DEPT INTERNAL MED 4,DIV NEUROL,NAGAKUTE,AICHI 48011,JAPAN

Doyu, M
论文数: 0 引用数: 0
h-index: 0
机构: AICHI MED UNIV,DEPT INTERNAL MED 4,DIV NEUROL,NAGAKUTE,AICHI 48011,JAPAN

Nakao, N
论文数: 0 引用数: 0
h-index: 0
机构: AICHI MED UNIV,DEPT INTERNAL MED 4,DIV NEUROL,NAGAKUTE,AICHI 48011,JAPAN

Shimada, N
论文数: 0 引用数: 0
h-index: 0
机构: AICHI MED UNIV,DEPT INTERNAL MED 4,DIV NEUROL,NAGAKUTE,AICHI 48011,JAPAN

Mitsuma, T
论文数: 0 引用数: 0
h-index: 0
机构: AICHI MED UNIV,DEPT INTERNAL MED 4,DIV NEUROL,NAGAKUTE,AICHI 48011,JAPAN

Maruyama, H
论文数: 0 引用数: 0
h-index: 0
机构: AICHI MED UNIV,DEPT INTERNAL MED 4,DIV NEUROL,NAGAKUTE,AICHI 48011,JAPAN

Kawakami, H
论文数: 0 引用数: 0
h-index: 0
机构: AICHI MED UNIV,DEPT INTERNAL MED 4,DIV NEUROL,NAGAKUTE,AICHI 48011,JAPAN

Nakamura, S
论文数: 0 引用数: 0
h-index: 0
机构: AICHI MED UNIV,DEPT INTERNAL MED 4,DIV NEUROL,NAGAKUTE,AICHI 48011,JAPAN
[66]
Correlation of peripheral nerve fiber loss and trinucleotide repeats in Machado-Joseph disease
[J].
Soong, B
;
Lin, KP
.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES,
1998, 25 (01)
:59-63

Soong, B
论文数: 0 引用数: 0
h-index: 0
机构:
Vet Gen Hosp, Neurol Inst, Taipei 11217, Taiwan Vet Gen Hosp, Neurol Inst, Taipei 11217, Taiwan

Lin, KP
论文数: 0 引用数: 0
h-index: 0
机构: Vet Gen Hosp, Neurol Inst, Taipei 11217, Taiwan
[67]
CLINICAL AND PATHOLOGICAL-STUDY OF A LARGE JAPANESE FAMILY WITH MACHADO-JOSEPH DISEASE TIGHTLY LINKED TO THE DNA MARKERS ON CHROMOSOME 14Q
[J].
TAKIYAMA, Y
;
OYANAGI, S
;
KAWASHIMA, S
;
SAKAMOTO, H
;
SAITO, K
;
YOSHIDA, M
;
TSUJI, S
;
MIZUNO, Y
;
NISHIZAWA, M
.
NEUROLOGY,
1994, 44 (07)
:1302-1308

TAKIYAMA, Y
论文数: 0 引用数: 0
h-index: 0
机构: JICHI MED SCH,DEPT NEUROL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN

OYANAGI, S
论文数: 0 引用数: 0
h-index: 0
机构: JICHI MED SCH,DEPT NEUROL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN

KAWASHIMA, S
论文数: 0 引用数: 0
h-index: 0
机构: JICHI MED SCH,DEPT NEUROL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN

SAKAMOTO, H
论文数: 0 引用数: 0
h-index: 0
机构: JICHI MED SCH,DEPT NEUROL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN

SAITO, K
论文数: 0 引用数: 0
h-index: 0
机构: JICHI MED SCH,DEPT NEUROL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN

YOSHIDA, M
论文数: 0 引用数: 0
h-index: 0
机构: JICHI MED SCH,DEPT NEUROL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN

TSUJI, S
论文数: 0 引用数: 0
h-index: 0
机构: JICHI MED SCH,DEPT NEUROL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN

MIZUNO, Y
论文数: 0 引用数: 0
h-index: 0
机构: JICHI MED SCH,DEPT NEUROL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN

NISHIZAWA, M
论文数: 0 引用数: 0
h-index: 0
机构: JICHI MED SCH,DEPT NEUROL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN
[68]
Positron emission tomography (PET) in Machado-Joseph disease
[J].
Taniwaki, T
;
Sakai, T
;
Kobayashi, T
;
Kuwabara, Y
;
Otsuka, M
;
Ichiya, Y
;
Masuda, K
;
Goto, I
.
JOURNAL OF THE NEUROLOGICAL SCIENCES,
1997, 145 (01)
:63-67

Taniwaki, T
论文数: 0 引用数: 0
h-index: 0
机构: NATL CHIKUGO HOSP,CHIKUGO,FUKUOKA 833,JAPAN

Sakai, T
论文数: 0 引用数: 0
h-index: 0
机构: NATL CHIKUGO HOSP,CHIKUGO,FUKUOKA 833,JAPAN

Kobayashi, T
论文数: 0 引用数: 0
h-index: 0
机构: NATL CHIKUGO HOSP,CHIKUGO,FUKUOKA 833,JAPAN

Kuwabara, Y
论文数: 0 引用数: 0
h-index: 0
机构: NATL CHIKUGO HOSP,CHIKUGO,FUKUOKA 833,JAPAN

Otsuka, M
论文数: 0 引用数: 0
h-index: 0
机构: NATL CHIKUGO HOSP,CHIKUGO,FUKUOKA 833,JAPAN

Ichiya, Y
论文数: 0 引用数: 0
h-index: 0
机构: NATL CHIKUGO HOSP,CHIKUGO,FUKUOKA 833,JAPAN

Masuda, K
论文数: 0 引用数: 0
h-index: 0
机构: NATL CHIKUGO HOSP,CHIKUGO,FUKUOKA 833,JAPAN

Goto, I
论文数: 0 引用数: 0
h-index: 0
机构: NATL CHIKUGO HOSP,CHIKUGO,FUKUOKA 833,JAPAN
[69]
Heterogeneous intracellular localization and expression of ataxin-3
[J].
Trottier, Y
;
Cancel, G
;
An-Gourfinkel, I
;
Lutz, Y
;
Weber, C
;
Brice, A
;
Hirsch, E
;
Mandel, JL
.
NEUROBIOLOGY OF DISEASE,
1998, 5 (05)
:335-347

Trottier, Y
论文数: 0 引用数: 0
h-index: 0
机构: ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

Cancel, G
论文数: 0 引用数: 0
h-index: 0
机构: ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

An-Gourfinkel, I
论文数: 0 引用数: 0
h-index: 0
机构: ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

Lutz, Y
论文数: 0 引用数: 0
h-index: 0
机构: ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

Weber, C
论文数: 0 引用数: 0
h-index: 0
机构: ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

Brice, A
论文数: 0 引用数: 0
h-index: 0
机构: ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

Hirsch, E
论文数: 0 引用数: 0
h-index: 0
机构: ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

Mandel, JL
论文数: 0 引用数: 0
h-index: 0
机构: ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France
[70]
POLYGLUTAMINE EXPANSION AS A PATHOLOGICAL EPITOPE IN HUNTINGTONS-DISEASE AND 4 DOMINANT CEREBELLAR ATAXIAS
[J].
TROTTIER, Y
;
LUTZ, Y
;
STEVANIN, G
;
IMBERT, G
;
DEVYS, D
;
CANCEL, G
;
SAUDOU, F
;
WEBER, C
;
DAVID, G
;
TORA, L
;
AGID, Y
;
BRICE, A
;
MANDEL, JL
.
NATURE,
1995, 378 (6555)
:403-406

TROTTIER, Y
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

LUTZ, Y
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

STEVANIN, G
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

IMBERT, G
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

DEVYS, D
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

CANCEL, G
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

SAUDOU, F
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

WEBER, C
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

DAVID, G
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

TORA, L
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

AGID, Y
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

BRICE, A
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

MANDEL, JL
论文数: 0 引用数: 0
h-index: 0
机构: ULP,CNRS,INSERM,INST GENET & BIOL MOLEC CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE