ライフサイエンスコーパス: Menkes

1 Menkes and Wilson diseases are associated with retinal d

2 Menkes ATPase (MNK) has been shown to transport cytosoli

3 Menkes ATPase is directly required for this copper efflu

4 Menkes disease and occipital horn syndrome (OHS) are all

5 Menkes disease and Wilson disease are human disorders of

6 Menkes disease arises from a genetic impairment in coppe

7 Menkes disease is a fatal neurodegenerative disorder due

8 Menkes disease is a fatal neurodegenerative disorder of

9 Menkes disease is a fatal neurodegenerative disorder of

10 Menkes disease is a fatal X-linked disorder of copper me

11 Menkes disease is a lethal neurodegenerative disorder of

12 Menkes disease is an X-linked recessive condition charac

13 Menkes disease, a fatal neurodegenerative disorder resul

14 Menkes is an infantile, fatal, hereditary copper-deficie

15 Menkes' disease (MD) and occipital horn syndrome (OHS) a

16 aspects of copper histidine treatment in 25 Menkes syndrome patients at the National Institutes of H

17 and mutant Wilson cDNAs were expressed in a Menkes copper transporter-deficient mottled fibroblast c

18 In this study, a Menkes disease mutation, G1019D, located in the large cy

19 RNA blot analysis revealed abundant Menkes gene expression in several cell lines, and immuno

20 is in the CNS, a polyclonal antisera against Menkes ATPase was used in immunoblot and immunohistochem

21 nction, intracellular copper metabolism, and Menkes ATPase abundance, localization and trafficking we

22 Cu incorporation into SOD in both normal and Menkes lymphoblasts, which is consistent with 64Cu incor

23 N-terminal domains of the Wilson's and Menkes disease proteins (N-WND and N-MNK) were overexpre

24 ting adenosine triphosphatases (Wilson's and Menkes disease proteins).

25 hallmark of pathologies such as Wilson's and Menkes diseases, various neurodegenerative diseases, and

26 Wilson disease (WD) and Menkes disease (MNK) are inherited disorders of copper m

27 Comparisons to the Wilson and Menkes disease A-domains reveal the presence of an addit

28 Finally, several mutations in the Wilson and Menkes disease ATPases occur in the A-domain, and their

29 ly and is homologous to the human Wilson and Menkes disease ATPases.

30 y the RAN1 gene is similar to the Wilson and Menkes disease proteins and yeast Ccc2 protein, which ar

31 rs Cu to metal-binding domains of Wilson and Menkes disease proteins in the cytoplasm.

32 that are homologous to the human Wilson and Menkes disease proteins.

33 s of Cu(2+)-ATPases, defective in Wilson and Menkes disease.

34 Wilson and Menkes diseases are genetic disorders of copper metaboli

35 Retinopathy in Wilson and Menkes diseases may result not only from abnormal system

36 amily, which includes the related Wilson and Menkes diseases proteins.

37 of various mutations that lead to Wilson and Menkes diseases.

38 was undertaken to assess retinal Wilson and Menkes expression and localization.

39 To determine whether the Wilson and Menkes genes may act locally in the retina, this study w

40 used to test for the presence of Wilson and Menkes mRNAs in mouse and human retinas and retinal pigm

41 The WND and Menkes proteins are distinguished from other P-type ATPa

42 caused by mutations in the Wilson (WND) and Menkes (MNK) copper-transporting P1B-type ATPases.

43 asis is connected to severe diseases such as Menkes and Wilson diseases, Alzheimer's disease, prion d

44 nd frequently fatal human disorders, such as Menkes disease and Friedreich's ataxia.

45 tment of copper deficiency disorders such as Menkes disease.

46 er 1) but also by the copper exporter ATP7A (Menkes ATPase), whose function is achieved through coppe

47 cc2, a P-type ATPase related to human ATP7A (Menkes disease protein) and ATP7B (Wilson disease protei

48 smin, from PN to Bergmann glia, where ATP7A (Menkes disease protein) is present.

49 ng domains (MBDs) of the two P-type ATPases (Menkes and Wilson disease proteins), the destination for

50 This is the case for both Menkes and Wilson disease, arising from mutations in ATP

51 This requirement is underscored by Menkes disease, a fatal neurodegenerative disorder of ch

52 This requirement in humans is underscored by Menkes disease, an X-linked copper deficiency disorder c

53 s in the copper (Cu) transporter ATP7A cause Menkes disease.

54 -transporting ATPases ATP7A and ATP7B cause Menkes disease and Wilson disease, respectively.

55 Defects in copper metabolism cause Menkes and Wilson's disease, myeloneuropathy, and cardio

56 ular copper homeostasis, and mutations cause Menkes and Wilson diseases, respectively.

57 Classic Menkes disease has a severe phenotype, with death in ear

58 ys using cultured fibroblasts from a classic Menkes disease patient all indicated small amounts of na

59 sence of supplemental copper and in cultured Menkes mutant fibroblasts exhibiting impaired copper eff

60 nd the effects of genetic copper deficiency (Menkes syndrome) and copper overload (Wilson disease).

61 arcinoma placental cell line, behaved as did Menkes fibroblasts by avidly absorbing copper but not re

62 defective in the copper deficiency disorder, Menkes disease.

63 n an untreatable neurodegenerative disorder, Menkes disease.

64 the copper deficiency and toxicity disorders Menkes and Wilson diseases caused by mutations in the p-

65 lead to severe neurodegenerative disorders, Menkes disease and Wilson disease, respectively.

66 er deficiency and copper toxicity disorders, Menkes and Wilson diseases, respectively.

67 cally distinct X-linked inherited disorders: Menkes disease and occipital horn syndrome (OHS).

68 s of ATP7A activity is associated with fatal Menkes disease and various other pathologies.

69 copper transporter and serve as a model for Menkes disease, provided an in vivo partial loss-of-func

70 well as the development of novel models for Menkes disease have permitted a greater understanding of

71 in the cloning of the genes responsible for Menkes syndrome and Wilson disease.

72 ether, these data reveal a critical role for Menkes ATPase in the availability of an NMDA receptor-de

73 Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CR

74 urons derived from mice lacking a functional Menkes ATPase demonstrated no copper release.

75 y disorders (i.e. anaemia, haemochromatosis, Menkes disease, Wilson's disease), and neurodegenerative

76 es related to intestinal copper homeostasis (Menkes Copper ATPase (Atp7a) and metallothionein) in the

77 Human Menkes disease and the murine Mottled phenotype are X-li

78 x type) that is closely related to the human Menkes and Wilson disease proteins was cloned.

79 ntaining the open reading frame of the human Menkes disease gene was constructed and used to transfor

80 g domains in the amino terminus of the human Menkes protein.

81 sporting P-type ATPases, including the human Menkes/Wilson proteins and yeast Ccc2p.

82 pathway, and expression of a wild type human Menkes cDNA complemented this defect, as evidenced by th

83 and oxaliplatin was investigated using human Menkes' disease fibroblasts (Me32a) that do not express

84 curative, the nature of the basic defect in Menkes syndrome suggests that corrective efforts are lik

85 The gene defective in Menkes disease (ATP7A) encodes a copper transporting P-t

86 n-superoxide dismutase (SOD) was examined in Menkes lymphoblasts that express a genetic defect of cop

87 SOD activity was approximately 40% higher in Menkes than normal lymphoblasts.

88 may ameliorate noradrenergic hypofunction in Menkes disease.

89 may ameliorate noradrenergic hypofunction in Menkes disease.

90 One, ATP7A, is the protein nonfunctional in Menkes disease.

91 Mutations in ATP7A result in Menkes disease, a disorder of copper metabolism.

92 The increased synthesis of SOD in Menkes lymphoblasts may play a protective role against c

93 inhibited 64Cu(II) incorporation into SOD in Menkes lymphoblasts under conditions in which no signifi

94 incorporation into newly synthesized SOD in Menkes lymphoblasts was approximately equal to the maxim

95 runcation that results in OHS rather than in Menkes disease.

96 a protective role against copper toxicity in Menkes lymphoblasts.

97 the proper folding of the MNK transporter in Menkes patients may be responsive to parenteral copper t

98 is of Cu-related genetic diseases, including Menkes disease and Wilson disease.

99 ss the gene for Wilson disease, thus linking Menkes and Wilson proteins to maternal delivery of coppe

100 a significant impairment in copper-mediated Menkes ATPase trafficking was observed in the absence of

101 an hereditary diseases of copper metabolism, Menkes syndrome and Wilson's disease, encode P-type ATPa

102 s of two classic disorders of Cu metabolism, Menkes disease and Wilson's disease, which paved the way

103 ditary diseases of copper metabolism, namely Menkes syndrome and Wilson's disease, encode P-type ATPa

104 copper-deficiency-related characteristics of Menkes disease and the copper-toxicity-related character

105 This in vivo correction of Menkes disease through the rescue of aberrant splicing m

106 The expression of Menkes cDNAs with successive mutations of the conserved

107 nts, we have identified a zebrafish model of Menkes disease termed calamity that results from splicin

108 etic studies identified a zebrafish model of Menkes disease that can be used for high-throughput ther

109 In a well-established mouse model of Menkes disease, mottled-brindled (mo-br), we tested whet

110 phenotype, OHS, rather than the phenotype of Menkes disease.

111 y the most important finding in the study of Menkes syndrome.

112 tabolic studies revealed that trafficking of Menkes ATPase after NMDA receptor activation is associat

113 t in the rapid and reversible trafficking of Menkes ATPase to neuronal processes, independent of the

114 lesclomol holds promise for the treatment of Menkes and associated disorders of hereditary copper def

115 cipital horn syndrome, an allelic variant of Menkes disease, have demonstrated that only this alterna

116 e liver, it is likely that the Wilson and/or Menkes proteins provide copper to ceruloplasmin made in

117 vels but also from loss of retinal Wilson or Menkes protein.

118 ering one Cu(I) ion to the Wilson's (WND) or Menkes disease protein (MNK).

119 diverse mutations lead to X-linked recessive Menkes disease or occipital horn syndrome.

120 he present study the full-length recombinant Menkes protein was shown by immunofluorescence to locali

121 rvation, immunofluorescent analysis revealed Menkes ATPase in the late Golgi of hippocampal neurons i

122 tled-brindled mouse-a murine model of severe Menkes disease.

123 Since Menkes lymphoblasts contain elevated copper levels, the

124 alization to synapses.SIGNIFICANCE STATEMENT Menkes and Wilson disease affect copper homeostasis and

125 re mutated in the copper imbalance syndromes Menkes disease and Wilson disease, respectively.

126 The Menkes and Wilson genes are homologous copper transporte

127 The Menkes and Wilson proteins were immunolocalized in human

128 The Menkes disease gene encodes a P-type transmembrane ATPas

129 The Menkes disease protein (ATP7A or MNK) is a P-type transm

130 The Menkes mRNA and protein were present in the RPE and neur

131 The Menkes protein (MNK; ATP7A) is a copper-transporting P-t

132 is process, which requires both Gef1 and the Menkes disease Cu2+-ATPase yeast homolog Ccc2, occurs in

133 ivery to P-type ATPases Atp7a and Atp7b (the Menkes and Wilson disease proteins, respectively), which

134 nctional and sequence similarity between the Menkes/Wilson copper export proteins and CCC2 in yeast,

135 Both the Menkes and Wilson proteins are present in the RPE.

136 The mouse homologues for the Menkes (MNK) and Wilson (WND) disease genes are the mott

137 protein can functionally substitute for the Menkes protein, supporting the concept that these protei

138 Mutations in WND and its homolog, the Menkes protein, lead to genetic disorders of copper meta

139 known intracellular location identified the Menkes ATPase in fractions similar to those containing t

140 for this protein and related domains in the Menkes and Wilson disease proteins.

141 y been shown to result from mutations in the Menkes disease gene (MNK), which encodes a copper-transp

142 membrane associated proteins, including the Menkes copper ATPase.

143 t that the copper-induced trafficking of the Menkes and Wilson disease copper ATPases is associated w

144 nzymes, ATP7A and ATP7B, the products of the Menkes and Wilson disease genes, respectively, catalyze

145 e time and dose-dependent trafficking of the Menkes ATPase from the Golgi compartment in response to

146 Although the localization of the Menkes ATPase was identical in Atox1(+/+) and Atox1(-/-)

147 at is localized between exons 1 and 2 of the Menkes disease gene (ATP7 A, MNK) at Xq13.3.

148 In order to investigate the role of the Menkes disease protein in copper transport, recombinant

149 To elucidate the function of the Menkes disease protein, a plasmid containing the open re

150 the PGAM 1 cDNA upstream from exon 2 of the Menkes gene is likely to be a processed pseudogene origi

151 dies against the amino-terminal third of the Menkes protein (ATP7A; MNK) by immunizing rabbits with a

152 icking between HAH1 and the first MBD of the Menkes protein (MNK1).

153 nce containing transmembrane domain 3 of the Menkes protein was found to be sufficient for localizati

154 These data demonstrate that the Menkes disease protein functions to deliver copper into

155 pper chaperone HAH1 transports copper to the Menkes and Wilson proteins, which are copper-translocati

156 Defects in ATP7A lead to Menkes disease or its milder variant, occipital horn syn

157 at is similar to the copper pumps related to Menkes and Wilson diseases and provides a useful prokary

158 disorders of intracellular copper transport, Menkes disease and Wilson disease.

159 e first conditional mutation associated with Menkes disease and demonstrate correction of the misloca

160 asis, ATP7A and ATP7B, genes associated with Menkes disease and Wilson disease, respectively, reveale

161 ound Cu-ATPase that has been identified with Menkes syndrome.

162 Atox1 interacts with Menkes disease protein and Wilson disease protein (WD) a

163 t combination in affected male newborns with Menkes disease.

164 detected in fibroblasts from a patient with Menkes disease or in Hep3B hepatocellular carcinoma cell

165 iciency was first delineated in persons with Menkes syndrome, advances in our understanding of the cl

166 in association with the generation of the WT Menkes protein in all rescued mutants.

167 yces cerevisiae deficient in CCC2, the yeast Menkes/Wilson disease gene homologue.