ライフサイエンスコーパス: sarcoglycan

1 k-in mice with an H77C substitution in alpha-sarcoglycan.

2 at arise from deficiencies in dystrophin and sarcoglycan.

3 ognition and processing of misfolded epsilon-sarcoglycan.

4 gp130-deficient mice had a decrease in alpha-sarcoglycan.

5 ial nuclear sequestration of beta- and gamma-sarcoglycan.

6 athy and muscular dystrophy that lacks delta-sarcoglycan.

7 ations in the genes encoding beta- and delta-sarcoglycan.

8 of the dystrophin-associated protein, gamma-sarcoglycan.

9 ighly related to gamma-sarcoglycan and delta-sarcoglycan.

10 tudies, and in transgenic mice lacking gamma-sarcoglycan.

11 ced in RNA that encodes a mutant human gamma-sarcoglycan.

12 ered with normal membrane targeting of gamma-sarcoglycan.

13 lead to the up-regulation of alpha- and beta-sarcoglycan.

14 ally expressed SGCE, which codes for epsilon-sarcoglycan.

15 regulation of beta, gamma, delta, or epsilon sarcoglycan.

16 B3, ERGIC3, PHF3, reticulocalbin-3, and beta-sarcoglycan.

17 omplex containing beta-, delta-, and epsilon-sarcoglycan.

18 ogy in AR-LGMD with primary mutations in the sarcoglycans.

19 ith either a complete or partial loss of the sarcoglycans.

20 rcolemma is dependent upon expression of the sarcoglycans.

21 s in one of the four genes coding for muscle sarcoglycans.

22 rosines on the intracellular portions of the sarcoglycans.

23 ds were conjugated with an antibody to gamma-sarcoglycan, a cardiomyocyte cell surface antigen, and m

24 a1 integrin (alpha7beta1-ITG) and with alpha-sarcoglycan, a member of the Dystrophin-Associated Glyco

25 related to the effects of decreased epsilon-sarcoglycan activity on the development or function of m

26 We injected recombinant beta- or delta-sarcoglycan adenoviruses into skeletal muscles of corres

27 A locus near the sarcoglycan alpha ( SGCA), rs4794106, was suggestive in

28 e restored to the sarcolemma including alpha-sarcoglycan, alpha-/beta-dystroglycan and sarcospan.

29 Mutations in additional DGC genes, the sarcoglycans, also lead to cardiomyopathy and muscular d

30 ycoproteins alpha-, beta-, gamma-, and delta-sarcoglycan and beta-dystroglycan were markedly decrease

31 sarcoglycan, that is highly related to gamma-sarcoglycan and delta-sarcoglycan.

32 d cardiomyopathy, we used mice lacking gamma-sarcoglycan and inserted a transgene that "rescued" gamm

33 The dystrophin-associated proteins alpha-sarcoglycan and neuronal nitric oxide synthase were also

34 into a complex with alpha-, beta- and delta-sarcoglycan and sarcospan.

35 ding allele expressed both this mutant alpha-sarcoglycan and the other components of the sarcoglycan-

36 These data suggest that increased gamma-sarcoglycan and/or mislocalization of gamma-sarcoglycan

37 that the dystrophin-associated proteins, the sarcoglycans and alpha-dystrobrevin, are critical for bo

38 nal dystrophin was confirmed by detection of sarcoglycans and neuronal nitric oxide synthase at the s

39 Interestingly, trace amounts of sarcoglycans and other DAPs can be detected at the mdx s

40 phin and many DAPs, including dystroglycans, sarcoglycans, and dystrobrevins, along myofibers.

41 Sarcospan is tightly linked to the sarcoglycans, and together these proteins form a subcomp

42 h laminin alpha2 chain, dystrophin, and beta-sarcoglycan are all part of the same adhesion complex, t

43 letal muscle of mice lacking gamma- or delta-sarcoglycan are less susceptible.

44 Sarcoglycans are a group of single-pass transmembrane gl

45 The sarcoglycans are known as an integral subcomplex of the

46 Dystrophin and its associated proteins, the sarcoglycans, are normally expressed in heart and skelet

47 aining showed extensive restoration of delta-sarcoglycan as well as alpha- and beta-sarcoglycan prote

48 glycan-specific antibody and found that zeta-sarcoglycan associated with other members of the sarcogl

49 ate with increased expression of utrophin or sarcoglycans, but rather caused their decreased expressi

50 ycan was found in the nucleus of S151A delta-sarcoglycan cardiomyocytes.

51 Cs were 35 times more efficient at restoring sarcoglycan compared with cultured myoblasts.

52 successful restoration of the cardiomyocyte sarcoglycan complex also eliminated coronary artery vasc

53 -sarcoglycan is an integral component of the sarcoglycan complex and, as such, is important in the pa

54 rcoglycan leads to a concomitant loss of the sarcoglycan complex as well as sarcospan and a dramatic

55 In addition, the adipose sarcoglycan complex associates with sarcospan and lamini

56 Restoration of the sarcoglycan complex at the plasma membrane requires rein

57 oglycan associated with other members of the sarcoglycan complex at the plasma membrane.

58 r with the myocytes, express a cell-specific sarcoglycan complex containing beta-, delta-, and epsilo

59 Loss of the dystrophin-sarcoglycan complex delocalizes nitric oxide synthase (N

60 t beta-sarcoglycan null mice, which lack the sarcoglycan complex in adipose tissue and skeletal muscl

61 suggested the presence of a distinct epsilon-sarcoglycan complex in skeletal muscle that was disrupte

62 gamma-sarcoglycan is also a component of the sarcoglycan complex in the smooth muscle.

63 ofibrils due to the loss of the dystroglycan-sarcoglycan complex in these mice.

64 mice, which neither show a disruption of the sarcoglycan complex in vascular smooth muscle nor vascul

65 our data demonstrate a novel function of the sarcoglycan complex in whole body glucose homeostasis an

66 The sarcoglycan complex is found normally at the plasma memb

67 coglycanopathies, this disintegration of the sarcoglycan complex may, in addition to the dystrophin c

68 -sarcoglycan hearts with perturbation of the sarcoglycan complex only within the adjacent myocytes.

69 ic defects in the plasma membrane-associated sarcoglycan complex produce cardiomyopathy characterized

70 The sarcoglycan complex resides at the muscle plasma membran

71 However, the vascular smooth muscle sarcoglycan complex was intact in the coronary arteries

72 in coronary arteries, and disruption of the sarcoglycan complex was observed in vascular smooth musc

73 The full sarcoglycan complex was restored in all subjects, and mu

74 A subcomplex within the DGC, the sarcoglycan complex, associates with dystrophin and medi

75 Disruption of the sarcoglycan complex, through primary gene mutations in d

76 made by ablating genes for components of the sarcoglycan complex, we show that long-term treatment wi

77 Sgce is a component of the dystrophin-sarcoglycan complex, Zac1 is a nuclear protein inducing

78 ar dystrophy are associated with a disrupted sarcoglycan complex.

79 as a component of the vascular smooth muscle sarcoglycan complex.

80 induce a correct localization of the dystro-sarcoglycan complex.

81 with dystrophin, alpha1-syntrophin, and the sarcoglycan complex.

82 at will permit normal assembly of the entire sarcoglycan complex.

83 y, function, and downstream signaling of the sarcoglycan complex.

84 s closely associated with the membrane-bound sarcoglycan complex.

85 scle fiber size, and restoration of the full sarcoglycan complex.

86 nsequence on the expression of the adipocyte sarcoglycan complex.

87 alpha-Sarcoglycan deficiency results in a severe form of muscu

88 beta-sarcoglycan-deficient (Sgcb-null) mice developed severe

89 both mdx (dystrophin mutant mice) and delta-sarcoglycan-deficient (Sgcd(-/-)) mouse models of diseas

90 alyzed protein expression of nNOS in several sarcoglycan-deficient animal models of muscular dystroph

91 and porcine MSCs for the treatment of delta-sarcoglycan-deficient dystrophic hamster muscle without

92 topathology showed increased fibrosis in the sarcoglycan-deficient hearts, but not in hearts lacking

93 H77C protein in striated muscle of the alpha-sarcoglycan-deficient mice prevented the disease.

94 e this secondary vasospasm, we treated gamma-sarcoglycan-deficient mice with the calcium channel anta

95 as a modifier of muscular dystrophy in gamma-sarcoglycan-deficient mice.

96 on is not a primary cause of beta- and delta-sarcoglycan-deficient muscular dystrophy.

97 ormal Ca(2)+ influx in dystrophin- and alpha-sarcoglycan-deficient myofibers leads to altered develop

98 esence of dystrophin at the sarcolemma, beta-sarcoglycan-deficient skeletal muscle presents with a di

99 ce integrin expression in mice lacking delta-sarcoglycan (delta sgc), a mouse model for human limb gi

100 ted virus (AAV) vectors carrying human delta-sarcoglycan (delta-SG) gene in TO-2 hamsters, a congesti

101 ardiac expression of a mutant of human delta-sarcoglycan (deltasg(S151A)), which has previously been

102 mice devoid of laminin alpha2 chain and beta-sarcoglycan (dy(3K)/Sgcb).

103 Expression of the sarcoglycans, dystroglycan and dystrophin has been confi

104 To answer this question, we generated delta-sarcoglycan/dystrophin double knockout mice (delta-Dko)

105 of mdx- (lacking dystrophin) or sgcd- (delta-sarcoglycan-encoding gene) null mice resulted in a signi

106 Additionally, sarcoglycan expression after transplantation should mark

107 currently unclear whether sub-physiological sarcoglycan expression also contributes to the mild phen

108 The absence of sarcoglycan expression in cardiomyocytes and skeletal my

109 mdx mice and (2) stable restoration of alpha-sarcoglycan expression in KO-SGCA mice by systemic injec

110 We speculate that low-level sarcoglycan expression may represent a useful strategy t

111 nd inserted a transgene that "rescued" gamma-sarcoglycan expression only in skeletal muscle.

112 Our results suggest that sub-physiological sarcoglycan expression plays a critical role in ameliora

113 Cardiomyocyte-specific sarcoglycan expression was sufficient to correct cardiac

114 pha-sarcoglycan locus caused a loss of alpha-sarcoglycan expression, resulting in muscular dystrophy

115 xed Neo-cassette led to recovered H77C alpha-sarcoglycan expression.

116 oglycan-null mice, we replaced cardiomyocyte sarcoglycan expression.

117 xpressing this transgene fully restore gamma-sarcoglycan expression.

118 gamma-Sarcoglycan, fibulin-2, and collagen XV were identified

119 nd extracellular domains of Drosophila delta-sarcoglycan for normal muscle structure and function.

120 oxyl-terminal dystrophin fragment and of the sarcoglycans from the sarcolemma during coxsackievirus B

121 riatum to compensate for the loss of epsilon-sarcoglycan function may rescue the motor deficits in DY

122 Loss of gamma-sarcoglycan (gamma-SG) induces muscle degeneration and s

123 rophy 2C is caused by mutations in the gamma-sarcoglycan gene (gsg) that results in loss of this prot

124 Drosophila deleted for the gamma/delta-sarcoglycan gene (Sgcd) develop progressive muscle and h

125 Here we show that the epsilon-sarcoglycan gene (Sgce) and Zac1 (Lot1) are both paterna

126 model and achieved efficient long-term delta-sarcoglycan gene expression and rescue of cardiac functi

127 this study was to attain long-lasting alpha-sarcoglycan gene expression in limb-girdle muscular dyst

128 Persistent alpha-sarcoglycan gene expression was achieved for 6 months in

129 Therefore, the S151A delta-sarcoglycan gene mutation acts in a dominant negative ma

130 Similar to the human delta-sarcoglycan gene mutation, S151A delta-sarcoglycan trans

131 In the heart, sarcoglycan gene mutations produce regional defects in m

132 to treat the majority of patients with gamma-sarcoglycan gene mutations.

133 Gene transfer of the corresponding deleted sarcoglycan gene preserved sarcolemmal integrity, preven

134 n line 840, deletion of the Drosophila delta-sarcoglycan gene produced disrupted flight muscles with

135 To study sarcoglycan gene replacement, we introduced transgenes e

136 ctors encoding either the lacZ gene or delta-sarcoglycan gene were constructed.

137 Mutation of the alpha-sarcoglycan gene, also a DGC component, causes LGMD2D an

138 840 contained a large deletion of the delta-sarcoglycan gene, and this line displayed progressive im

139 patient has a primary mutation in the gamma-sarcoglycan gene, which causes premature truncation of g

140 (LGMD 2E) is caused by mutations in the beta-sarcoglycan gene, which is expressed in skeletal, cardia

141 y autosomal recessive mutations in the alpha-sarcoglycan gene.

142 ed progressively larger regions of the delta-sarcoglycan gene.

143 Mutations in sarcoglycan genes lead to muscular dystrophy and cardiom

144 genes, while in mammals there are additional sarcoglycan genes that probably arose from gene duplicat

145 In invertebrates, there are three sarcoglycan genes, while in mammals there are additional

146 1 genes are located in intron 8 of the alpha-sarcoglycan genes.

147 ll as patients with primary mutations in the sarcoglycan genes.

148 strophies caused by primary mutations in the sarcoglycan genes.

149 diseases caused by primary mutations in the sarcoglycan genes.

150 ull mouse models, we show that loss of alpha-sarcoglycan has no consequence on the expression of the

151 tes from mice lacking either gamma- or delta-sarcoglycan have normal compliance.

152 deficient in dystrophin and, less so, delta-sarcoglycan have reduced survival during in vivo dobutam

153 was intact in the coronary arteries of gamma-sarcoglycan hearts with perturbation of the sarcoglycan

154 ogical benefits to correct the loss of gamma-sarcoglycan in a Drosophila model, in heterologous cell

155 First, we show the presence of gamma-sarcoglycan in a number of smooth muscle-containing orga

156 his complex, dystrophin in mdx mice or alpha sarcoglycan in Sgca(-/-) mice, results in the spontaneou

157 -dystroglycan, alpha-dystroglycan, and alpha-sarcoglycan in skeletal muscle fibers from mdx mice.

158 The specificity of the expression of gamma-sarcoglycan in smooth muscle was confirmed by analysis o

159 ar spasm, while restoration of smooth muscle sarcoglycan in the background of sarcoglycan-null allele

160 The distribution of epsilon-sarcoglycan in the mouse brain suggests that the symptom

161 Retention of delta-sarcoglycan in the nucleus was accompanied by partial nu

162 To analyze whether the loss of epsilon-sarcoglycan in the striatum alone causes abnormal nuclea

163 The results suggest that the loss of epsilon-sarcoglycan in the striatum contributes to motor deficit

164 imply a potential role for disruption of the sarcoglycans in an acquired form of heart failure.

165 We previously demonstrated that loss of sarcoglycans in smooth muscle leads to constrictions of

166 toring a deficient structural protein (delta-sarcoglycan) in the cardiomyopathic (CM) hamster evaluat

167 r muscle fiber transduction other than alpha-sarcoglycan included expression of major histocompatibil

168 In striated muscle, sarcoglycans interact with dystrophin and other dystroph

169 term filamin 2 (FLN2), as a gamma- and delta-sarcoglycan interacting protein.

170 thout affecting assembly of the mutant gamma-sarcoglycan into a complex with alpha-, beta- and delta-

171 ntroduced transgenes expressing murine gamma-sarcoglycan into muscle of normal mice.

172 Sarcoglycan is a membrane-associated protein complex fou

173 Here, we demonstrate that gamma-sarcoglycan is also a component of the sarcoglycan compl

174 Together, these data demonstrate that zeta-sarcoglycan is an integral component of the sarcoglycan

175 y in mice lacking gamma-sarcoglycan or delta-sarcoglycan is characterized by focal damage.

176 diomyopathy and that the C-terminus of gamma-sarcoglycan is critical for the functioning of the entir

177 o the case that the behavior of mutant alpha-sarcoglycan is different between humans and mice, mutant

178 truncation of a transmembrane protein gamma-sarcoglycan is functional.

179 epsilon-Sarcoglycan is located at the plasma membrane in neurons

180 In the central nervous system, epsilon-sarcoglycan is widely expressed in neurons of the cerebr

181 neration of specific muscles when one of the sarcoglycans is deficient, as well as preliminary inform

182 we show that expression of three out of four sarcoglycans is not sufficient to maintain nNOS at the s

183 Overexpression of gamma-sarcoglycan lead to the up-regulation of alpha- and beta

184 However, loss of beta- or delta-sarcoglycan leads to a concomitant loss of the sarcoglyc

185 The neuroanatomical distribution of epsilon-sarcoglycan-like immunoreactivity in mouse was investiga

186 nimals also had an 80-85% reduction in alpha-sarcoglycan localization in these muscles, indicating co

187 cassette retained at the targeted H77C alpha-sarcoglycan locus caused a loss of alpha-sarcoglycan exp

188 ee different alleles at the Drosophila delta-sarcoglycan locus.

189 dystrophy contributes to the development of sarcoglycan-mediated cardiomyopathy, we used mice lackin

190 muscle defects are independent processes in sarcoglycan-mediated muscular dystrophies and, as such,

191 ild-type protein, disease-associated epsilon-sarcoglycan missense mutations (H36P, H36R and L172R) pr

192 High expression levels of epsilon-sarcoglycan mRNA and immunoreactivity were found in the

193 mmunohistochemistry, coexpression of epsilon-sarcoglycan mRNA and tryptophan hydroxylase immunoreacti

194 The expression of epsilon-sarcoglycan mRNA was studied by a sensitive fluorescence

195 lization of tyrosine hydroxylase and epsilon-sarcoglycan mRNAs within all the midbrain dopaminergic (

196 evaluated the coronary vasculature of gamma-sarcoglycan mutant mice and found microvascular filling

197 for regeneration was seen in this Drosophila sarcoglycan mutant.

198 s to and promotes the degradation of epsilon-sarcoglycan mutants when both proteins are co-expressed.

199 transgenic mice that express the S151A delta-sarcoglycan mutation in the heart using the alpha-myosin

200 herapeutic option not only for patients with sarcoglycan mutations, but also for patients with idiopa

201 fferentially regulated genes and ESTs, delta-sarcoglycan, myosin Va, FK506-binding protein 51 (FKBP51

202 ardiomyocytes with donor-derived nuclei were sarcoglycan-negative.

203 thological and enhances disease in the delta-sarcoglycan null (Sgcd(-/-)) mouse model of muscular dys

204 We further demonstrate that beta-sarcoglycan null mice, which lack the sarcoglycan comple

205 skeletal muscle of previously created alpha-sarcoglycan null mice.

206 Using multiple sarcoglycan null mouse models, we show that loss of alph

207 Mammalian sarcoglycan null muscle was also found to exhibit exerci

208 hin-glycoprotein complex-lacking Scgd (delta-sarcoglycan) null mouse, indicating that dysferlin funct

209 ed Cn activation in the context of the delta-sarcoglycan-null (scgd(-/-)) mouse model of limb-girdle

210 t the dystrophic phenotype observed in delta-sarcoglycan-null (Sgcd(-/-)) mice and dystrophin mutant

211 d the dystrophic phenotype observed in delta-sarcoglycan-null (Sgcd(-/-)) mice through a mechanism in

212 demonstrated that introduction of the gamma-sarcoglycan-null allele onto the DBA/2J background confe

213 ooth muscle sarcoglycan in the background of sarcoglycan-null alleles did not.

214 scle and transplanted these cells into delta-sarcoglycan-null dystrophic mice.

215 Gamma-sarcoglycan-null mice expressing this transgene fully re

216 Echocardiography of verapamil-treated, gamma-sarcoglycan-null mice showed an improvement in left vent

217 To test this hypothesis, we crossed gamma-sarcoglycan-null mice, a model of limb-girdle muscular d

218 ansgene rescue strategy in the background of sarcoglycan-null mice, we replaced cardiomyocyte sarcogl

219 lycan-null/Col6a2Deltaex5 mice than in gamma-sarcoglycan-null mice.

220 ibutes to skeletal muscle pathology in gamma-sarcoglycan-null mice.

221 reduced muscle pathology compared with gamma-sarcoglycan-null mice.

222 ale mice were transplanted into female delta-sarcoglycan-null mice.

223 We found that the resulting gamma-sarcoglycan-null/Col6a2Deltaex5 mice indeed exhibit redu

224 metric tetanic force are even lower in gamma-sarcoglycan-null/Col6a2Deltaex5 mice than in gamma-sarco

225 Cardiomyopathy in mice lacking gamma-sarcoglycan or delta-sarcoglycan is characterized by foc

226 Marked gamma-sarcoglycan overexpression produced cytoplasmic aggregat

227 y failed to express sarcoglycan, with only 2 sarcoglycan-positive fibers detected in the quadriceps m

228 ce for the regeneration of large clusters of sarcoglycan-positive muscle fibers, which were protected

229 in and the associated membrane proteins, the sarcoglycans, produce muscular dystrophy and cardiomyopa

230 The absence of delta-sarcoglycan produces microinfarcts in heart and skeletal

231 pports a model where dystrophin, but not the sarcoglycans, protects the cardiac myocyte against mecha

232 Tyr(6) in the intracellular region of gamma-sarcoglycan protein (gamma-SG) was necessary for proper

233 rtion of the cytoplasmic region of the delta-sarcoglycan protein and left intact the transmembrane an

234 FISH revealed a wide distribution of epsilon-sarcoglycan protein and mRNA throughout the mouse brain.

235 We generated an internally truncated gamma-sarcoglycan protein that we have termed Mini-Gamma by de

236 blasts, AMMC-derived muscle fibers expressed sarcoglycan protein throughout their entire length, cons

237 soform, brain-specific SGCE mRNA and epsilon-sarcoglycan protein were detected in iPSC-derived contro

238 y revealed a similar distribution of epsilon-sarcoglycan protein.

239 eved to result from mutations of the epsilon-sarcoglycan protein.

240 ed by using an antiserum against the epsilon-sarcoglycan protein.

241 There are six known sarcoglycan proteins in mammals whereas there are only t

242 delta-sarcoglycan as well as alpha- and beta-sarcoglycan proteins to the myocyte membranes, despite l

243 pha 2 laminin congenital muscular dystrophy, sarcoglycan-related muscular dystrophy, and alpha 7 inte

244 F result from the loss of dystrophin and the sarcoglycans, respectively.

245 een humans and mice, mutant human R77C alpha-sarcoglycan restored the expression of the sarcoglycan-s

246 utations in alpha-, beta-, delta-, and gamma-sarcoglycan result in autosomal recessive limb girdle mu

247 The sarcoglycan-sarcospan and dystroglycan complexes were di

248 he association of gamma-sarcoglycan with the sarcoglycan-sarcospan complex by biochemical analysis an

249 We report that loss of the sarcoglycan-sarcospan complex in muscle causes a dramati

250 -sarcoglycan and the other components of the sarcoglycan-sarcospan complex in striated muscle, and di

251 Loss of the sarcoglycan-sarcospan complex in vascular smooth muscle

252 tration that membrane expression of a mutant sarcoglycan-sarcospan complex is insufficient in prevent

253 Indeed, sustained expression of intact sarcoglycan-sarcospan complex was noted at the sarcolemm

254 a-sarcoglycan restored the expression of the sarcoglycan-sarcospan complex when introduced by adenovi

255 of the disease, leading to disruption of the sarcoglycan-sarcospan complex.

256 s critical for the functioning of the entire sarcoglycan-sarcospan complex.

257 structural determinants required for proper sarcoglycan-sarcospan expression and function.

258 Mice lacking delta-sarcoglycan (Scgd(-/-) mice) showed markedly less dystro

259 (dystrophin gene) and deletion of the delta-sarcoglycan (Scgd) gene.

260 n-/-) deletion in mice nullizygous for delta-sarcoglycan (scgd-/-), a model of limb-girdle muscular d

261 loss of this protein, and disruption of the sarcoglycan (SG) complex.

262 LGMD) 2F is caused by mutations in the delta-sarcoglycan (SG) gene.

263 n the skeletal muscles of mice lacking alpha sarcoglycan (Sgca), a mouse model for limb girdle muscul

264 bated the muscle disease phenotypes in delta-sarcoglycan (Sgcd(-/-)), Dysf(-/-), and mdx mouse models

265 e, mutations in the gene encoding varepsilon-sarcoglycan (SGCE) cause the neurogenic movement disorde

266 d R102X) in the maternally imprinted epsilon-sarcoglycan (SGCE) gene and analysed properties such as

267 17 myoclonus-dystonia patients with epsilon-sarcoglycan (SGCE) gene mutation and 21 age- and sex-mat

268 The syndrome is related to epsilon-sarcoglycan (SGCE) gene mutations in about half the typi

269 Mutations in the gene encoding epsilon-sarcoglycan (SGCE) have been found in some patients with

270 one newly identified target exon in epsilon sarcoglycan (Sgce) showed that both RNA elements distrib

271 king the dystrophin-associated protein gamma-sarcoglycan (Sgcg null) was subjected to a lengthening p

272 mesoderm-specific transcript), Sgce (epsilon-sarcoglycan), Snrpn (small nuclear ribonucleoprotein pol

273 We generated a zeta-sarcoglycan-specific antibody and found that zeta-sarcog

274 mbrane requires reintroduction of the mutant sarcoglycan subunit in a manner that will permit normal

275 ociation, the function of dystrophin and the sarcoglycan subunits may differ.

276 ough primary gene mutations in dystrophin or sarcoglycan subunits, produces membrane instability and

277 s concurrent reduction of dystrophin and the sarcoglycans, suggesting that these proteins, like those

278 Recessive mutations of delta-sarcoglycan that eliminate expression, and therefore fun

279 entified a novel mammalian sarcoglycan, zeta-sarcoglycan, that is highly related to gamma-sarcoglycan

280 removal of 4 of the 7 coding exons in gamma-sarcoglycan, this approach provides a viable strategy to

281 -sarcoglycan and/or mislocalization of gamma-sarcoglycan to the cytoplasm is sufficient to induce mus

282 Thus, virus-mediated gene transfer of sarcoglycans to skeletal muscle in combination with phar

283 delta-sarcoglycan gene mutation, S151A delta-sarcoglycan transgenic mice developed dilated cardiomyop

284 Mice expressing high levels of gamma-sarcoglycan, under the control of the muscle-specific cr

285 zeta-Sarcoglycan was also found as a component of the vascula

286 Gamma-sarcoglycan was expressed in skeletal muscle under the c

287 d of placement at the plasma membrane, delta-sarcoglycan was found in the nucleus of S151A delta-sarc

288 g-term, sustainable gene expression of alpha-sarcoglycan was observed following gene transfer mediate

289 ultracentrifugation demonstrated that delta-sarcoglycan was physically dissociated from dystrophin w

290 missense mutation in the gene encoding delta-sarcoglycan was previously shown to associate with dilat

291 Additionally, zeta-sarcoglycan was reduced at the membrane in muscular dyst

292 ly glycosylated alpha dystroglycan and alpha sarcoglycan was reduced in mdx RMS, whereas dystrophin e

293 However, a marker of the DG complex, alpha-sarcoglycan, was specifically excluded from lipid raft d

294 ociated mutations on the function of epsilon-sarcoglycan we examined the biosynthesis and trafficking

295 sarcospan is integrally associated with the sarcoglycans, we screened >50 autosomal recessive muscul

296 knockout mice (delta-Dko) in which residual sarcoglycans were completely eliminated from the sarcole

297 These findings indicate that the alpha-sarcoglycan with the most frequent missense mutation in

298 rovide evidence for the association of gamma-sarcoglycan with the sarcoglycan-sarcospan complex by bi

299 r-derived nuclei generally failed to express sarcoglycan, with only 2 sarcoglycan-positive fibers det

300 , which causes premature truncation of gamma-sarcoglycan without affecting assembly of the mutant gam

301 We identified a novel mammalian sarcoglycan, zeta-sarcoglycan, that is highly related to