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Expression of Presenilin 1 mRNA in Rat Peripheral Organs and Brain

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Abstract

At least 50 different mutations in the presenilin 1 gene have been shown to cause early onset familial Alzheimer's disease. Although presenilin 1 has an obvious role in the pathogenesis of Alzheimer's disease, its function is still unknown. In the present study, the occurrence and distribution of presenilin 1 mRNA was examined in rat peripheral organs as well as in the brain by in situ hybridization histochemistry, using a radiolabelled oligonucleotide probe. In comparison to the brain, a high presenilin 1 mRNA expression was found in the testis, kidney, spleen, adrenal gland and thymus. It was also observed in skeletal muscle, liver, small intestine and lung, whereas no presenilin 1 could be detected in the heart, spinal cord and pancreas. Since presenilin 1 mRNA was found to be abundant in peripheral tissues which apparently are not affected in Alzheimer's disease, additional functions of presenilin 1 are suggested, unrelated to its role in the pathological processes of the disease.

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References cited

  • Benkovic SA, McGowan EM, Rothwell NJ, Hutton M, Morgan DG, Gordon MN (1997) Regional and cellular localization of presenilin-2 RNA in rat and human brain. Exp Neurol 45: 555-564.

    Google Scholar 

  • Berezovska O, Xia M, Page K, Wasco W, Tanzi RE, Hyman BT (1997) Developmental regulation of presenilin mRNA expression parallels notch expression. J Neuropath Exp Neurol 56: 40-44.

    Google Scholar 

  • Citron M, Westaway D, Xia W, Carlson G, Diehl T, Levesque G, Johnson-Wood K, Lee M, Seubert P, Davis A, Kholodenko D, Motter R, Sherrington R, Perry B, Yao H, Strome R, Lieberburg, I, Rommen SJ, Kim S, Schenk D, Fraser P, St George Hyslop P, Selkoe DJ (1997) Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nature Med 3: 67-72.

    Google Scholar 

  • Cribbs DH, Chen L-S, Bende SM, Laferla FM (1996) Widespread neuronal expression of the presenilin-1 early-onset Alzheimer's disease gene in the murine brain. Am J Path 148: 1797-1806.

    Google Scholar 

  • Dagerlind, Å, Friberg K, Bean AJ, Hökfelt T (1992) Sensitive mRNA detection using unfixed tissue: combined radioactive and nonradioactive in situ hybridization histochemistry. Histochemistry 98: 39-49.

    Google Scholar 

  • De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven F (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391: 387-390.

    Google Scholar 

  • Doan A, Thinakaran G, Borchelt DR, Slunt HH, Ratovitsky T, Podlisny M, Selkoe DJ, Seeger M, Gandy SE, Price DL, Sisodia SS (1996) Protein topology of presenilin 1. Neuron 17: 1023-1030.

    Google Scholar 

  • Duff K, Eckman C, Zehr C, Yu X, Prada C-M, Perez-Tur J, Hutton M, Buee L, Harigaya Y, Yager D, Morgan D, Gordon MN, Holcomb L, Refolo L, Zenk B, Hardy J, Younkin S (1996) Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1. Nature 383: 710-713.

    Google Scholar 

  • Elder GA, Tezapsidis N, Carter J, Shioi J, Bouras C, Li HC, Johnston JM, Efthimiopoulos S, Friedrich VL, Robakis NK (1996) Identification and neuron specific expression of the S182/presenilin I protein in human and rodent brains. J Neuroscience 45: 308-320.

    Google Scholar 

  • Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Roques P, Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349: 704-706.

    Google Scholar 

  • Hardy J (1997) Amyloid, the presenilins and Alzheimer's disease. Trends Neurol Sci 20: 154-159.

    Google Scholar 

  • Huynh DP, Ho VV, Pulst SM (1996) Characterization and expression of presenilin 1 in mouse brain. Neuroreport 7: 2423-2428.

    Google Scholar 

  • Kovacs DM, Fausett HJ, Page KJ, Kim T-W, Moir RD, Merriam DE, Hollister RD, Hallmark OG, Mancini R, Felsenstein KM, Hyman BT, Tanzi RE, Wasco W (1996) Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells. Nature Med 2: 224-229.

    Google Scholar 

  • Lee MK, Slunt HH, Martin LJ, Thinakaran G, Kim G, Gandy SE, Seeger M, Koo E, Price DL, Sisodia SS (1996) Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues. J Neurosci 16: 7513-7525.

    Google Scholar 

  • Lehmann S, Chiesa R, Harris DA (1997) Evidence for a six-transmembrane domain structure of presenilin 1. J Biol Chem 272: 12047-12051.

    Google Scholar 

  • Levitan D, Greenwald I (1995) Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature 377: 351-354.

    Google Scholar 

  • Levitan D, Doyle TG, Brousseau D, Lee MK, Thinakaran G, Slunt HH, Sisoida SS, Greenwald I (1996) Assessment of normal and mutant human presenilin function in Caenorhabditis elegans. Proc Natl Acad Sci USA 93: 14940-14944.

    Google Scholar 

  • Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu C-E, Jondro PD, Schmidt SD, Wang K, Crowley AC, Fu Y-H, Guenette SY, Galas D, Nemens E, Wijsman EM, Bird TD, Schellenberg GD, Tanzi RE (1995) Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 269: 973-977.

    Google Scholar 

  • Moussaoui S, Czech C, Pradier L, Blanchard V, Bonici B, Gohin M, Imperato A, Revah F (1996) Immunohistochemical analysis of presenilin-1 expression in the mouse brain. FEBS Letters 383: 219-222.

    Google Scholar 

  • Page K, Hollister R, Tanzi RE, Hyman BT (1996) In situ hybridization analysis of presenilin 1 mRNA in Alzheimer disease and in lesioned rat brain. Proc Natl Acad Sci USA 93: 14020-14024.

    Google Scholar 

  • Quarteronet D, Pradier L, Czech C, Delalonde L, Burgevin M-C, Doble A, Petitet F (1996) Localization of presenilin-1 mRNA in rat brain. Neuroreport 7: 2587-2591.

    Google Scholar 

  • Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T, Mar L, Sorbi S, Nacmias B, Piacentini S, Amaducci L, Chumakov I, Cohen D, Lannfelt L, Fraser PE, Rommens JM, St George-Hyslop PH (1995) Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376: 775-778.

    Google Scholar 

  • Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, Larson E, Levy-Lahad E, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt L, Selkoe D, Younkin S (1996) Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nature Med 2: 864-869.

    Google Scholar 

  • Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HAR, Haines JL, Pericak-Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St George-Hyslop PH (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375: 754-760.

    Google Scholar 

  • Slunt HH, Thinakaran G, Lee MK, Sisodia SS (1995) Nucleotide sequence of the chromosome 14-encoded S182 cDNA and revised secondary structure prediction. Int J Exp Clin Invest 2: 188-190.

    Google Scholar 

  • Suzuki T, Nishiyama K, Murayama S, Yamamoto A, Sato S, Kanazawa I, Sakaki Y (1996) Regional and cellular Presenilin I gene expression in human and rat tissues. Biochem Biophys Res Com 219: 708-713.

    Google Scholar 

  • Takahashi H, Murayama M, Takashima A, Mercken M, Nakazato, Y, Noguchi K, Imahori K (1996) Molecular cloning and expression of the rat homologue of presenilin-1. Neurosci Letters 206: 113-116.

    Google Scholar 

  • Takami K, Kazuhiro T, Matsuo A, Walker DG, McGeer PL (1997) Expression of presenilin-1 and-2 mRNAs in rat and Alzheimer's disease brains. Brain Res 748: 122-130.

    Google Scholar 

  • Tanzi RE, Gusella JF, Watkins PC, Bruns GAP, St George-Hyslop P, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, Neve RL (1987) Amyloid β protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235: 880-884.

    Google Scholar 

  • Tomita T, Maruyama K, Saido TC, Kume H, Shinozaki K, Tokuhiro S, Capell A, Walter J, Grünberg J, Haass C, Iwatsubo T, Obata K (1997) The presenilin 2 mutation (N141I) linked to familial Alzheimer disease (Volga German families) increases the secretion of amyloid beta protein ending at the 42nd (or 43rd) residue. Proc Natl Acad Sci USA 94: 2025-2030.

    Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Division of Geriatric Medicine, Karolinska Institute, S-141 86, Huddinge, Sweden

    Camilla Nilsberth, Lars Lannfelt & Marianne Schultzberg

  2. Cell Biology, Preclinical R&D, Astra Arcus AB, S-151 85, Södertälje, Sweden

    Johan Luthman

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  1. Camilla Nilsberth
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  2. Johan Luthman
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  3. Lars Lannfelt
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  4. Marianne Schultzberg
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Nilsberth, C., Luthman, J., Lannfelt, L. et al. Expression of Presenilin 1 mRNA in Rat Peripheral Organs and Brain. Histochem J 31, 515–523 (1999). https://doi.org/10.1023/A:1003887922777

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