Disruption of the β-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E

被引:174
作者
Durbeej, M
Cohn, RD
Hrstka, RF
Moore, SA
Allamand, V
Davidson, BL
Williamson, RA
Campbell, KP [1 ]
机构
[1] Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Physiol & Biophys, Iowa City, IA 52242 USA
[2] Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Neurol, Iowa City, IA 52242 USA
[3] Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Obstet & Gynecol, Iowa City, IA 52242 USA
[4] Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Pathol, Iowa City, IA 52242 USA
[5] Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Internal Med, Iowa City, IA 52242 USA
关键词
D O I
10.1016/S1097-2765(00)80410-4
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
Limb-girdle muscular dystrophy type 2E (LGMD 2E) is caused by mutations in the beta-sarcoglycan gene, which is expressed in skeletal, cardiac, and smooth muscle. beta-sarcoglycan-deficient (Sgcb-null) mice developed severe muscular dystrophy and cardiomyopathy with focal areas of necrosis. The sarcoglycan-sarcospan and dystroglycan complexes were disrupted in skeletal, cardiac, and smooth muscle membranes. epsilon-sarcoglycan was also reduced in membrane preparations of striated and smooth muscle. Loss of the sarcoglycan-sarcospan complex in vascular smooth muscle resulted in vascular irregularities in heart, diaphragm, and kidneys. Further biochemical characterization suggested the presence of a distinct epsilon-sarcoglycan complex in skeletal muscle that was disrupted in Sgcb-null mice. Thus, perturbation of vascular function together with disruption of the epsilon-sarcoglycan-containing complex represents a novel mechanism in the pathogenesis of LGMD 2E.
引用
收藏
页码:141 / 151
页数:11
相关论文
共 45 条
  • [1] Mild congenital muscular dystrophy in two patients with an internally deleted laminin alpha 2-chain
    Allamand, V
    Sunada, Y
    Salih, MAM
    Straub, V
    Ozo, CO
    AlTuraiki, MHS
    Akbar, M
    Kolo, T
    Colognato, H
    Zhang, X
    Sorokin, LM
    Yurchenco, PD
    Tryggvason, K
    Campbell, KP
    [J]. HUMAN MOLECULAR GENETICS, 1997, 6 (05) : 747 - 752
  • [2] Loss of the sarcoglycan complex and sarcospan leads to muscular dystrophy in β-sarcoglycan-deficient mice
    Araishi, K
    Sasaoka, T
    Imamura, M
    Noguchi, S
    Hama, H
    Wakabayashi, E
    Yoshida, M
    Hori, T
    Ozawa, E
    [J]. HUMAN MOLECULAR GENETICS, 1999, 8 (09) : 1589 - 1598
  • [3] BAHRON RJ, 1988, NEW ENGL J MED, V319, P15
  • [4] BARRESI R, 1999, IN PRESS J MED GEN
  • [5] LGMD 2E in Tunisia is caused by a homozygous missense mutation in β-sarcoglycan exon 3
    Bönnemann, CG
    Wong, J
    Ben Hamida, C
    Ben Hamida, M
    Hentati, F
    Kunkel, LM
    [J]. NEUROMUSCULAR DISORDERS, 1998, 8 (3-4) : 193 - 197
  • [6] Genomic screening for beta-sarcoglycan gene mutations: Missense mutations may cause severe limb-girdle muscular dystrophy type 2E (LGMD 2E)
    Bonnemann, CG
    PassosBueno, MR
    McNally, EM
    Vainzof, M
    Moreira, ED
    Marie, SK
    Pavanello, RCM
    Noguchi, S
    Ozawa, E
    Zatz, M
    Kunkel, LM
    [J]. HUMAN MOLECULAR GENETICS, 1996, 5 (12) : 1953 - 1961
  • [7] BETA-SARCOGLYCAN (A3B) MUTATIONS CAUSE AUTOSOMAL RECESSIVE MUSCULAR-DYSTROPHY WITH LOSS OF THE SARCOGLYCAN COMPLEX
    BONNEMANN, CG
    MODI, R
    NOGUCHI, S
    MIZUNO, Y
    YOSHIDA, M
    GUSSONI, E
    MCNALLY, EM
    DUGGAN, DJ
    ANGELINI, C
    HOFFMAN, EP
    OZAWA, E
    KUNKEL, LM
    [J]. NATURE GENETICS, 1995, 11 (03) : 266 - 273
  • [8] Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: A novel mechanism for cardiomyopathy and muscular dystrophy
    Coral-Vazquez, R
    Cohn, RD
    Moore, SA
    Hill, JA
    Weiss, RM
    Davisson, RL
    Straub, V
    Barresi, R
    Bansal, D
    Hrstka, RF
    Williamson, R
    Campbell, KP
    [J]. CELL, 1999, 98 (04) : 465 - 474
  • [9] Membrane targeting and stabilization of sarcospan is mediated by the sarcoglycan subcomplex
    Crosbie, RH
    Lebakken, CS
    Holt, KH
    Venzke, DP
    Straub, V
    Lee, JC
    Grady, RM
    Chamberlain, JS
    Sanes, JR
    Campbell, KP
    [J]. JOURNAL OF CELL BIOLOGY, 1999, 145 (01) : 153 - 165
  • [10] CROSBIE RH, 1998, FEBS LETT, V427, P270