Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein

Chelly, Jamel; Tümer, Zeynep; Tønnesen, T.; Petterson, Anne; Ishikawa-Brush, Yumiko; Tommerup, Niels; Horn, Nina; Monaco, Anthony P.

doi:10.1038/ng0193-14

Cited by 675 publications

(348 citation statements)

References 29 publications

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“…It appears in a presumed membranespanning helical region and may participate in the conformational change responsible for opening and closing the transport channel (1-4). For the Menkes sequence (23)(24)(25) and four of the bacterial examples (8,21,22) shown, this proline residue is between cysteines that are thought to provide metal coordination (4,21). The cysteines are not found in the KdpB K+-ATPase sequence (6), nor in the other two cyanobacterial ATPase sequences, PacL and Pmal (8,9).…”

Section: Discussionmentioning

confidence: 99%

P-type ATPase from the cyanobacterium Synechococcus 7942 related to the human Menkes and Wilson disease gene products.

Phung

Ajlani

Haselkorn

1994

Proc. Natl. Acad. Sci. U.S.A.

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7).The number of identified P-type ATPases is growing rapidly. In the course of cloning other genes from Synechococcus 7942, we found one that appears to encode a P-type ATPase. During the preparation of this paper three other cyanobacterial P-type ATPase sequences were published (8, 9). The first of these new reports concerns two genes for P-type ATPases from the same Synechococcus strain used in this study (8). However, the sequences of these genes differ significantly from the one we describe here. In addition, biochemical evidence indicates that the Synechococcus plasma membrane contains a P-type ATPase (10).We (Pharmacia), was selected on plates containing kanamycin at 50 ug/ml. For selective growth of E. coli strain DH5a (GIBCO/BRL) carrying antibiotic-resistance plasmids, ampicillin at 100 pug/ml or tetracycline 12 pig/ml was used.Cloning and Sequence Determination. Standard molecular genetic techniques, including DNA isolation, restriction nuclease digestion and ligation, and Southern and Northern blotting, were as described by Sambrook et al. (13). Genomic DNA was prepared from cells of Synechococcus 7942 according to Brusslan (14). RNA isolation was as described by Schaefer and Golden (15). A fragment containing part of the ctaA gene was isolated from a two-step size-fractionated Synechococcus DNA library. Synechococcus genomic DNA was first digested with BamHI and the restriction fiagments were separated by electrophoresis in an agarose gel. Fragments of 3-6 kb were isolated and digested with HindIII. Fragments of 2-3 kb were isolated, cloned into plasmid pBR322, and transformed into E. coli strain DH5a. Clone pLP180 (containing a 2.6-kb HindIII-BamHI fiagment) was identified by screening individual plasmid DNAs with an E. coli fabE (16) fragment as probe. A 320-bp Pst I-BamHI fragment was isolated from the HindIII-BamHI insert of pLP180 and used as probe to screen a library of wild-type Synechococcus genomic DNA in the cosmid vector pWB79 (prepared by J. Brusslan, University of Chicago). A 7-kb HindIll fragment was identified and smaller restriction nuclease fragments from it were subcloned into pUC18 and pBluescript vectors (Stratagene).Subclones for sequencing were generated either by nested deletion using the Erase-a-base kit (Promega) or by digesting the original clones with appropriate restriction nucleases and religating. Sequencing was done on both strands by the dideoxy chain-termination method with Sequenase version 2.0 (United States Biochemical) with either M13 universal and reverse primers or synthetic oligonucleotide primers. Fig. 1 summarizes the physical map of the 7-kb HindIII fragment and the 4.5-kb HindIII-EcoRV region within it that was sequenced completely on both strands.Insertional Inactivation of the ctaA Gene. The kanamycinresistance cassette from pUC4K was inserted between the Bgl II and Pst I sites of pLP1.5 (a pUC18-derived plasmid

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Section: Discussionmentioning

confidence: 99%

P-type ATPase from the cyanobacterium Synechococcus 7942 related to the human Menkes and Wilson disease gene products.

Phung

Ajlani

Haselkorn

1994

Proc. Natl. Acad. Sci. U.S.A.

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“…The defective gene in Menkes' disease (MNK) has been cloned and shown to encode a metal-binding ATPase that.is localized to the trans-Golgi [8][9][10][11]. It is therefore suspected that in Menkes' disease patients, the absence of this ATPase prevents some form of copper transport.…”

Section: Introductionmentioning

confidence: 99%

Delivering copper within plant cells

Himelblau¹

2000

Current Opinion in Plant Biology

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“…Further analysis of the biochemical changes in the tx mouse liver will assist understanding of copper transport and add to the knowledge of this process, which is increasing rapidly following the cloning of the genes affected in Menkes disease and Wilson disease [11][12][13][14][15]. In this paper we use radioactive copper, zinc and nickel to detect possible alterations in metal-binding polypeptides in the tx mutant using Western blots.…”

Section: Introductionmentioning

confidence: 99%

Decreased carbonic anhydrase III levels in the liver of the mouse mutant ‘toxic milk’ (tx) due to copper accumulation

Grimes

Paynter

Walker

et al. 1997

Biochemical Journal

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The mouse mutant ‘toxic milk‘ (tx) is characterized by marked hepatic accumulation of copper, similar to that found in patients with the genetic disorder of copper transport, Wilson disease. In addition, lactating tx females produce copper-deficient milk. To characterize further the biochemical basis of this defect, Western blots of tissue extracts from normal and tx mice were probed with various heavy-metal radioisotopes (63Ni, 65Zn and 64Cu). A 30 kDa Ni/Zn-binding polypeptide was found to be markedly decreased in the livers of the tx mice. This protein was isolated from normal adult mice using a procedure based on Ni-chelation chromatography. The amino acid sequences of two CNBr peptides were identical with portions of the mouse skeletal muscle carbonic anhydrase III (CAIII) sequence. Two other peptides sequenced had closely related sequences to that of CAIII, but with two differences in 45 amino acids. These two peptides may be derived from a novel CAIII isoform, which we term CAIIIB to distinguish it from the published form, CAIIIA. We isolated a cDNA clone corresponding to CAIIIA and used this to show that CAIIIA mRNA was also decreased in the mutant liver, but not in muscle. Copper loading of normal mice also decreased hepatic CAIIIA mRNA, suggesting that the decrease in CAIII mRNA in the tx mouse liver is a secondary consequence of the high copper levels in the liver.

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Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein

Cited by 675 publications

References 29 publications

P-type ATPase from the cyanobacterium Synechococcus 7942 related to the human Menkes and Wilson disease gene products.

P-type ATPase from the cyanobacterium Synechococcus 7942 related to the human Menkes and Wilson disease gene products.

Delivering copper within plant cells

Decreased carbonic anhydrase III levels in the liver of the mouse mutant ‘toxic milk’ (tx) due to copper accumulation

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