Androgen receptor mutation in Kennedy's disease

被引：30

作者：

Fischbeck, KH ^{[1
]}

Lieberman, A

Bailey, CK

Abel, A

Merry, DE

机构：

[1] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA

[2] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA

来源：

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES | 1999年 / 354卷 / 1386期

关键词：

polyglutamine disease; motor neuron disease; androgen receptor;

D O I：

10.1098/rstb.1999.0461

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Kennedy's disease is an X-linked form of motor neuron disease caused by an expanded polyglutamine repeat in the androgen receptor. While the expansion mutation causes some loss of transcriptional activity by the androgen receptor, the predominant effect of expansion is probably a toxic gain of function, similar to the mechanism of other polyglutamine expansion diseases. Features of the neurodegenerative phenotype of Kennedy's disease have now been reproduced in transgenic animals and neuronal cell culture. Nuclear inclusions of mutant androgen receptor protein are found in these model systems and in autopsy samples from patients with Kennedy's disease.

引用

页码：1075 / 1078

页数：4

共 26 条

[1] Abel A, 1998, AM J HUM GENET, V63, pA319
[2] STABILITY OF AN EXPANDED TRINUCLEOTIDE REPEAT IN THE ANDROGEN RECEPTOR GENE IN TRANSGENIC MICE
BINGHAM, PM
SCOTT, MO
WANG, SP
MCPHAUL, MJ
WILSON, EM
GARBERN, JY
MERRY, DE
FISCHBECK, KH
[J]. NATURE GENETICS, 1995, 9 (02) : 191 - 196
[3] Characterization of an expanded glutamine repeat androgen receptor in a neuronal cell culture system
Brooks, BP
Paulson, HL
Merry, DE
SalazarGrueso, EF
Brinkmann, AO
Wilson, EM
Fischbeck, KH
[J]. NEUROBIOLOGY OF DISEASE, 1997, 3 (04) : 313 - 323
[4] Brooks BP, 1998, J NEUROCHEM, V70, P1054
[5] Reduced androgen receptor gene expression with first exon CAG repeat expansion
Choong, CS
Kemppainen, JA
Zhou, ZX
Wilson, EM
[J]. MOLECULAR ENDOCRINOLOGY, 1996, 10 (12) : 1527 - 1535
[6] Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation
Davies, SW
Turmaine, M
Cozens, BA
DiFiglia, M
Sharp, AH
Ross, CA
Scherzinger, E
Wanker, EE
Mangiarini, L
Bates, GP
[J]. CELL, 1997, 90 (03) : 537 - 548
[7] Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain
DiFiglia, M
Sapp, E
Chase, KO
Davies, SW
Bates, GP
Vonsattel, JP
Aronin, N
[J]. SCIENCE, 1997, 277 (5334) : 1990 - 1993
[8] Kennedy's disease: Caspase cleavage of the androgen receptor is a crucial event in cytotoxicity
Ellerby, LM
Hackam, AS
Propp, SS
Ellerby, HM
Rabizadeh, S
Cashman, NR
Trifiro, MA
Pinsky, L
Wellington, CL
Salvesen, GS
Hayden, MR
Bredesen, DE
[J]. JOURNAL OF NEUROCHEMISTRY, 1999, 72 (01) : 185 - 195
[9] Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo
Ikeda, H
Yamaguchi, M
Sugai, S
Aze, Y
Narumiya, S
Kakizuka, A
[J]. NATURE GENETICS, 1996, 13 (02) : 196 - 202
[10] PROGRESSIVE PROXIMAL SPINAL AND BULBAR MUSCULAR ATROPHY OF LATE ONSET - A SEX-LINKED RECESSIVE TRAIT
KENNEDY, WR
ALTER, M
SUNG, JH
[J]. NEUROLOGY, 1968, 18 (07) : 671 - &

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