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PMID: 7568134 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 20 ·1995-09-26 ·Pages 9368-72

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Abstract

Transgenic Caenorhabditis elegans nematodes have been engineered to express potentially amyloidic human proteins. These animals contain constructs in which the muscle-specific unc-54 promoter/enhancer of C. elegans drives the expression of the appropriate coding regions derived from human cDNA clones. Animals containing constructs expressing the 42-amino acid beta-amyloid peptide (derived from human amyloid precursor protein cDNA) produce muscle-specific deposits immunoreactive with anti-beta-amyloid polyclonal and monoclonal antibodies. A subset of these deposits also bind the amyloid-specific dye thioflavin S, indicating that these deposits have the tinctural characteristics of classic amyloid. Co-expression of beta-peptide and transthyretin, a protein implicated in preventing the formation of insoluble beta-amyloid, leads to a dramatic reduction in the number of dye-reactive deposits. These results suggest that this invertebrate model may be useful for in vivo investigation of factors that modulate amyloid formation.

MeSH Terms
Amyloid beta-Peptides/biosynthesis,genetics,metabolism Animals Animals, Genetically Modified Antibodies, Monoclonal Base Sequence Benzothiazoles Caenorhabditis/metabolism Chimera DNA Primers Epitopes/analysis Fluorescent Dyes/metabolism Genotype Humans Immunohistochemistry Male Molecular Sequence Data Prealbumin/biosynthesis,genetics Recombinant Fusion Proteins/biosynthesis,metabolism Restriction Mapping Thiazoles/metabolism
Chemicals
Amyloid beta-Peptides Antibodies, Monoclonal Benzothiazoles DNA Primers Epitopes Fluorescent Dyes Prealbumin Recombinant Fusion Proteins Thiazoles thioflavin T
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Link C D
Department of Biological Sciences, University of Denver, CO 80208, USA.
References (41)
41 references, click to expand
  1. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein.
    Biochem Biophys Res Commun. 1984 May 16;120(3):885-90 PMID: 6375662
  2. Theoretical models of the ion channel structure of amyloid beta-protein.
    Biophys J. 1994 Dec;67(6):2137-45 PMID: 7535109
  3. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors.
    Nature. 1988 Feb 11;331(6156):525-7 PMID: 2893289
  4. A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions.
    Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 PMID: 3045756
  5. Familial amyloidotic polyneuropathy.
    Trends Neurosci. 1989 Mar;12(3):88-92 PMID: 2469222
  6. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type.
    Science. 1990 Jun 1;248(4959):1124-6 PMID: 2111584
  7. A modular set of lacZ fusion vectors for studying gene expression in Caenorhabditis elegans.
    Gene. 1990 Sep 14;93(2):189-98 PMID: 2121610
  8. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.
    Nature. 1991 Feb 21;349(6311):704-6 PMID: 1671712
  9. The transthyretin cDNA sequence is normal in transthyretin-derived senile systemic amyloidosis.
    FEBS Lett. 1991 Apr 9;281(1-2):177-80 PMID: 2015890
  10. Formation of beta-amyloid protein deposits in brains of transgenic mice.
    Nature. 1991 Jul 18;352(6332):239-41 PMID: 1906990
  11. Deposits of amyloid beta protein in the central nervous system of transgenic mice.
    Science. 1991 Jul 19;253(5017):323-5 PMID: 1857970
  12. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease.
    Science. 1991 Oct 4;254(5028):97-9 PMID: 1925564
  13. Peptides homologous to the amyloid protein of Alzheimer's disease containing a glutamine for glutamic acid substitution have accelerated amyloid fibril formation.
    Biochem Biophys Res Commun. 1991 Sep 30;179(3):1247-54 PMID: 1681804
  14. Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences.
    EMBO J. 1991 Dec;10(12):3959-70 PMID: 1935914
  15. Expression of the human beta-amyloid protein of Alzheimer's disease specifically in the brains of transgenic mice.
    J Biol Chem. 1991 Nov 15;266(32):21331-4 PMID: 1939169
  16. Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene.
    Nature. 1991 Oct 31;353(6347):844-6 PMID: 1944558
  17. An improved thioflavine S method for staining neurofibrillary tangles and senile plaques in Alzheimer's disease.
    Experientia. 1992 Jan 15;48(1):8-10 PMID: 1371102
  18. Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid.
    Neurosci Lett. 1992 Feb 3;135(2):235-8 PMID: 1625800
  19. Light and electron microscopic localization of beta-amyloid protein in muscle biopsies of patients with inclusion-body myositis.
    Am J Pathol. 1992 Jul;141(1):31-6 PMID: 1321564
  20. Characterization of Caenorhabditis elegans lectin-binding mutants.
    Genetics. 1992 Aug;131(4):867-81 PMID: 1516818
  21. Fibril formation by primate, rodent, and Dutch-hemorrhagic analogues of Alzheimer amyloid beta-protein.
    Biochemistry. 1992 Nov 10;31(44):10716-23 PMID: 1420187
  22. Deposition of beta/A4 immunoreactivity and neuronal pathology in transgenic mice expressing the carboxyl-terminal fragment of the Alzheimer amyloid precursor in the brain.
    Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10857-61 PMID: 1438289
  23. Familial amyloidosis.
    J Intern Med. 1992 Dec;232(6):525-7 PMID: 1474359
  24. Molecular characterization of the her-1 gene suggests a direct role in cell signaling during Caenorhabditis elegans sex determination.
    Genes Dev. 1993 Feb;7(2):216-28 PMID: 8436294
  25. Activation of the c-Ki-ras oncogene in aflatoxin B1-induced hepatocellular carcinoma and adenoma in the rat: detection by denaturing gradient gel electrophoresis.
    Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2045-9 PMID: 8446626
  26. Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state.
    J Neurosci. 1993 Apr;13(4):1676-87 PMID: 8463843
  27. Synthetic peptides corresponding to different mutated regions of the amyloid gene in familial Creutzfeldt-Jakob disease show enhanced in vitro formation of morphologically different amyloid fibrils.
    Proc Natl Acad Sci U S A. 1993 May 15;90(10):4451-4 PMID: 8506284
  28. Cerebrospinal fluid inhibits Alzheimer beta-amyloid fibril formation in vitro.
    Ann Neurol. 1993 Oct;34(4):631-3 PMID: 8215255
  29. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice [corrected].
    Nat Genet. 1993 Sep;5(1):22-30 PMID: 8220418
  30. Sequestration of amyloid beta-peptide.
    Ann N Y Acad Sci. 1993 Sep 24;695:139-43 PMID: 8239272
  31. Expression of the human beta-amyloid precursor protein gene from a yeast artificial chromosome in transgenic mice.
    Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10578-82 PMID: 8248147
  32. Secondary structure of amyloid beta peptide correlates with neurotoxic activity in vitro.
    Mol Pharmacol. 1994 Mar;45(3):373-9 PMID: 8145724
  33. Transgenic mouse brain histopathology resembles early Alzheimer's disease.
    Ann Neurol. 1994 May;35(5):598-607 PMID: 7513982
  34. Amyloid beta protein-induced neuronal cell death: neurotoxic properties of aggregated amyloid beta protein.
    Brain Res. 1994 Mar 14;639(2):240-4 PMID: 7515762
  35. Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3.
    J Clin Invest. 1994 Aug;94(2):860-9 PMID: 8040342
  36. Transthyretin sequesters amyloid beta protein and prevents amyloid formation.
    Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8368-72 PMID: 8078889
  37. Unifying features of systemic and cerebral amyloidosis.
    Mol Neurobiol. 1994 Feb;8(1):49-64 PMID: 7916192
  38. Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments.
    Nature. 1994 Nov 3;372(6501):92-4 PMID: 7969426
  39. Alzheimer's disease and soluble A beta.
    Neurobiol Aging. 1994 Mar-Apr;15(2):143-52 PMID: 7838284
  40. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.
    Nature. 1995 Feb 9;373(6514):523-7 PMID: 7845465
  41. A new method for predicting signal sequence cleavage sites.
    Nucleic Acids Res. 1986 Jun 11;14(11):4683-90 PMID: 3714490
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.20.9368
Published
1995-09-26
Pages
9368-72
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC40986
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.20.9368 PMC Full Text View journal details
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