Abstract
We have investigated the cDNA sequence of the copper-transporting P-type ATPase (Atp7a) gene of the macular mouse, a model for human Menkes disease. A point mutation (T to C) that results in substitution of proline for serine in a putative eighth transmembrane domain of the ATP7A was identified. This contrasts with abnormalities identified in the Atp7a of other mottled mouse strains: lack of expression of Atp7a mRNA in the dappled mouse, and a splicing mutation in the blotchy mouse.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Boison D, Stoffel W (1989) Myelin-deficient rat: a point mutation in exon III (A → C, Thr75 → Pro) of the myelin proteolipid protein causes dysmyelination and oligodendrocyte death. EMBO J 8, 3295–3302
Camakaris J, Danks DM, Ackland L, Cartright E, Borger P, Cotton RGH (1980) Altered copper metabolism in cultured cells from human Menkes’ syndrome and mottled mouse mutants. Biochem Genet 18, 117–131
Cecchi C, Avner P (1996) Genomic organization of the mottled gene, the mouse homologue of the human Menkes disease gene. Genomics 37, 96–104
Chelly J, Turner Z, Tonnesen T, Petterson A, Ishikawa-Brush Y, Tommerup N, Horn N, Monaco AP (1993) Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein. Nature Genet 3, 14–19
Das S, Levinson B, Whitney S, Vulpe C, Packman S (1994) Diverse mutations in patients with Menkes disease often lead to exon skipping. Am J Hum Genet 55, 883–889
Das S, Levinson B, Vulpe C, Whitney S, Gitschier J, Packman S (1995) Similar splicing mutations of the Menkes/mottled copper-transporting ATPase gene in occipital horn syndrome and the blotchy mouse. Am J Hum Genet 56, 570–576
Drews D, Drohan WN, Lubon H (1994) Transgenic detection in mouse tail digests. BioTechniques 17, 866–867
Gencic S, Hudson LD (1990) Conservative ammo acid substitution in the myelin proteolipid protein of jimpymsd mice. J Neurosci 10, 117–124
Gencic S, Abuelo D, Ambler M, Hudson LD (1989) Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein. Am J Hum Genet 45, 435–442
George AM, Reed V, Glenister P (1994) Analysis of Mnk, the murine homologue of the locus for Menkes disease, in normal and mottled (Mo) mice. Genomics 22, 27–35
Goka TJ, Stevenson RE, Hefferan PM, Howell RR (1976) Menkes’ disease: a biochemical abnormality in cultured human fibroblasts. Proc Natl Acad Sci USA 73, 604–606
Green MC (1989) Catalog of mutant genes and polymorphic loci. In: Genetic Variants and Strains of the Laboratory Mouse, Lyon MF, Searle AG (eds). (Oxford: Oxford University Press), pp 241–244
Horn N (1976) Copper incorporation studies on cultured cells for prenatal diagnosis of Menkes’ disease. Lancet 1, 1156–1158
Hudson LD, Puckett C, Berndt J, Chan J, Gencic S (1989) Mutation of the proteolipid protein gene PLP in a human X chromosome-linked myelin disorder. Proc Natl Acad Sci USA 86, 8128–8131
Iwase T, Nishimura M, Sugimura H, Igarashi H, Ozawa F, Shinmura K, Suzuki M, Tanaka M, Kino I (1996) Localization of Menkes gene expression in the mouse brain; its association with neurological manifestations in Menkes model mice. Acta Neuropathol 91, 482–488
Kaler SG (1994) Menkes disease. Adv Pediatr 41, 263–304
Kaler SG, Gallo LK, Proud VK, Percy AK, Mark Y, Segal NA, Goldstein DS, Holmes CS, Gahl WA (1994) Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus. Nature Genet 8, 195–202
Katsura T, Kawasaki H, Yamano T, Shimada M (1988) Copper contents and pathological changes in various organs of macular mouse. Congenital Anom 28, 85
Kodama H, Abe T, Takama M, Takahashi I, Kodama M, Nishimura M (1993) Histochemical localization of copper in the intestine and kidney of macular mice: light and electron microscopic study. J Histochem Cytochem 41, 1529–1535
Levinson B, Vulpe C, Elder B, Martin C, Verley F (1994) The mottled gene is the mouse homologue of the Menkes disease gene. Nature Genet 6, 369–373
Lytton J, MacLennan DH (1988) Molecular cloning of cDNAs from human kidney coding for two alternatively spliced products of the cardia Ca2+-ATPase gene. J Biol Chem 263, 15024–15031
Menkes JHM, Alter M, Steigleder GK, Weakley DR, Sung JH (1962) A sex-linked recessive disorder with retardation of growth, pericular hair and focal cerebellar degeneration. Pediatrics 29, 764–779
Mercer JF, Livingston J, Hall B, Paynter JA, Begy C, Chandrasekharappa S, Lockhart P, Grimes A, Bhave M, Siemieniak D, Glover TW (1993) Isolation of a partial candidate gene for Menkes disease by positional cloning. Nature Genet 3, 20–25
Mercer JF, Grimes A, Ambrosini L (1994) Mutation sin the murine homologue of the Menkes gene in dappled and blotchy mice. Nature Genet 6, 374–378
Nishimura M (1975) A new mutant mouse macular (MI) (in Japanese). Exp Anim 24, 185
Petris MJ, Mercer JFB, Culvenor JG, Lockhart P, Gleeson PA, Camakaris, J (1996) Ligand-regulated transport of the Menkes copper P-type ATPase efflux pump from the Golgi apparatus to the plasma membrane: a novel mechanism of regulated trafficking. EMBO J 15, 6084–6095
Pham-Dinh D, Popot JL, Boespflug-Tanguy O, Landrieu P, Deleuze JF, Boue J, Jolies P, Dautigny A (1991) Pelizaeus-Merzbacher disease: a valine to phenylalanine point mutation in a putative extracellular loop of myelin proteolipid. Proc Natl Acad Sci USA 88, 7562–7566
Pratt VM, Trofatter JA, Schinzel A, Dlouhy SR, Conneally PM, Hodes ME (1991) A new mutation in the proteolipid protein (PLP) gene in a German family with Pelizaeus-Merzbacher disease. Am J Med Genet 38, 136–139
Strehler EE, Strehler-Page MA, Vogel G, Carafoli E (1989) mRNAs for plasma membrane calcium pump isoforms differing in their regulatory domain are generated by alternative slicing that involves two internal donor sites in a single exon. Proc Natl Acad Sci USA 86, 6908–6912
Suter U, Moskow JJ, Welcher AA, Snipes GJ, Kosaras B, Sidman RL, Buchberg AM, Shooter EM (1992a). A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse. Proc Natl Acad Sci USA 89, 4382–4386
Suter U, Welcher AA, Ozcelik T, Snipes GJ, Kosaras B, Francke U, Billings-Gagliardi S, Sidman RL, Shooter EM (1992b) Trembler mouse carries a point mutation in a myelin gene. Nature 356, 241–244
Trofatter JA, Dlouhy SR, DeMyer W, Conneally PM, Hodes ME (1989) Pelizaseus-Merzbacher disease: tight linkage to proteolipid protein gene exon variant. Proc Natl Acad Sci USA 86, 9427–9430
Valentijn LJ, Baas F, Wolterman RA, Hoogendijk JE, van den Bosch NH, Zorn I, Gabreels-Festen AW, de Visser M, Bolhuis PA (1992) Identical point mutations of PMP-22 in Trembler-J mouse and Charcot-Marie-Tooth disease type 1A. Nature Genet 2, 288–291
Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J(1993) Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nature Genet 3, 7–13
Yamaguchi Y, Heiny ME, Suzuki M, Gitlin JD (1996) Biochemical characterization and intracellular localization of the Menkes disease protein. Proc Natl Acad Sci USA 93, 14030–14035
Yamano T, Shimada M, Kawasaki H, Onaga A, Nishimura M (1987) Clinicopathological study on macular mutant mouse. Acta Neuropathol (berl) 72, 256–260
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mori, M., Nishimura, M. A serine-to-proline mutation in the copper-transporting P-type ATPase gene of the macular mouse. Mammalian Genome 8, 407–410 (1997). https://doi.org/10.1007/s003359900457
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s003359900457