CA2309383A1 - Genes a expression reduite dans les neurones mesencephaliques dopaminergiques - Google Patents
Genes a expression reduite dans les neurones mesencephaliques dopaminergiques Download PDFInfo
- Publication number
- CA2309383A1 CA2309383A1 CA002309383A CA2309383A CA2309383A1 CA 2309383 A1 CA2309383 A1 CA 2309383A1 CA 002309383 A CA002309383 A CA 002309383A CA 2309383 A CA2309383 A CA 2309383A CA 2309383 A1 CA2309383 A1 CA 2309383A1
- Authority
- CA
- Canada
- Prior art keywords
- nucleic acid
- gene
- ptx3
- expression
- neurological
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 136
- 230000014509 gene expression Effects 0.000 title claims abstract description 80
- 210000005064 dopaminergic neuron Anatomy 0.000 title claims abstract description 19
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 70
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 66
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 66
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 40
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 36
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 26
- 208000020016 psychiatric disease Diseases 0.000 claims abstract description 26
- 239000012634 fragment Substances 0.000 claims abstract description 24
- 208000020925 Bipolar disease Diseases 0.000 claims abstract description 21
- 208000028683 bipolar I disease Diseases 0.000 claims abstract description 21
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 20
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims abstract description 19
- 230000000926 neurological effect Effects 0.000 claims abstract description 13
- 210000004027 cell Anatomy 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 54
- 102000004169 proteins and genes Human genes 0.000 claims description 49
- 210000002569 neuron Anatomy 0.000 claims description 43
- 241001465754 Metazoa Species 0.000 claims description 28
- 108010048671 Homeodomain Proteins Proteins 0.000 claims description 26
- 241000282414 Homo sapiens Species 0.000 claims description 19
- 230000035772 mutation Effects 0.000 claims description 12
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 10
- 239000013598 vector Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 239000013604 expression vector Substances 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 4
- 230000037430 deletion Effects 0.000 claims description 4
- 238000012217 deletion Methods 0.000 claims description 4
- 230000037431 insertion Effects 0.000 claims description 3
- 238000003780 insertion Methods 0.000 claims description 3
- 108700028369 Alleles Proteins 0.000 claims description 2
- 238000003259 recombinant expression Methods 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 14
- 208000019022 Mood disease Diseases 0.000 abstract description 12
- 206010012335 Dependence Diseases 0.000 abstract description 11
- 230000003291 dopaminomimetic effect Effects 0.000 abstract description 5
- 230000007171 neuropathology Effects 0.000 abstract description 2
- 239000002299 complementary DNA Substances 0.000 description 27
- 210000004556 brain Anatomy 0.000 description 26
- 238000009396 hybridization Methods 0.000 description 22
- 102000009331 Homeodomain Proteins Human genes 0.000 description 21
- 241000699666 Mus <mouse, genus> Species 0.000 description 19
- 230000018109 developmental process Effects 0.000 description 19
- 108020004414 DNA Proteins 0.000 description 18
- 238000011161 development Methods 0.000 description 18
- 230000001105 regulatory effect Effects 0.000 description 18
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 13
- 238000010367 cloning Methods 0.000 description 13
- 238000011065 in-situ storage Methods 0.000 description 12
- 210000003523 substantia nigra Anatomy 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 10
- 238000009739 binding Methods 0.000 description 10
- 230000027455 binding Effects 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 210000001259 mesencephalon Anatomy 0.000 description 9
- 238000003752 polymerase chain reaction Methods 0.000 description 9
- 210000004515 ventral tegmental area Anatomy 0.000 description 9
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 8
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 150000001413 amino acids Chemical group 0.000 description 8
- 238000010171 animal model Methods 0.000 description 8
- 229960003638 dopamine Drugs 0.000 description 8
- 230000001537 neural effect Effects 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000009261 transgenic effect Effects 0.000 description 8
- 101150020229 Apcs gene Proteins 0.000 description 7
- 230000004568 DNA-binding Effects 0.000 description 7
- 101150031628 PITX2 gene Proteins 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 230000004069 differentiation Effects 0.000 description 7
- 230000013020 embryo development Effects 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 230000001817 pituitary effect Effects 0.000 description 7
- 238000001514 detection method Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 238000011813 knockout mouse model Methods 0.000 description 6
- 239000013603 viral vector Substances 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 238000011144 upstream manufacturing Methods 0.000 description 5
- 108700005087 Homeobox Genes Proteins 0.000 description 4
- 101150026563 NR4A2 gene Proteins 0.000 description 4
- 101150092239 OTX2 gene Proteins 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 210000005013 brain tissue Anatomy 0.000 description 4
- 230000007850 degeneration Effects 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 230000033001 locomotion Effects 0.000 description 4
- 210000001161 mammalian embryo Anatomy 0.000 description 4
- 238000003127 radioimmunoassay Methods 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 241001573498 Compacta Species 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 108700005077 Viral Genes Proteins 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 230000003925 brain function Effects 0.000 description 3
- 210000002308 embryonic cell Anatomy 0.000 description 3
- 210000002257 embryonic structure Anatomy 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 238000012239 gene modification Methods 0.000 description 3
- 230000005017 genetic modification Effects 0.000 description 3
- 235000013617 genetically modified food Nutrition 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 101100048438 Caenorhabditis elegans unc-30 gene Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000829171 Hypocrea virens (strain Gv29-8 / FGSC 10586) Effector TSP1 Proteins 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 208000019430 Motor disease Diseases 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 101100350576 Mus musculus Otx1 gene Proteins 0.000 description 2
- 241000244206 Nematoda Species 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 108010069820 Pro-Opiomelanocortin Proteins 0.000 description 2
- 239000000683 Pro-Opiomelanocortin Substances 0.000 description 2
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 101000725492 Rattus norvegicus Pro-opiomelanocortin Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 108700019146 Transgenes Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 238000000376 autoradiography Methods 0.000 description 2
- 230000003376 axonal effect Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 238000012411 cloning technique Methods 0.000 description 2
- 239000003184 complementary RNA Substances 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 210000002451 diencephalon Anatomy 0.000 description 2
- 210000004002 dopaminergic cell Anatomy 0.000 description 2
- 206010013663 drug dependence Diseases 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 230000007257 malfunction Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 210000001706 olfactory mucosa Anatomy 0.000 description 2
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 2
- 238000000059 patterning Methods 0.000 description 2
- 230000009465 prokaryotic expression Effects 0.000 description 2
- 230000006916 protein interaction Effects 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 2
- 210000001202 rhombencephalon Anatomy 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 210000001587 telencephalon Anatomy 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 238000001086 yeast two-hybrid system Methods 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- 108020004463 18S ribosomal RNA Proteins 0.000 description 1
- 108020005096 28S Ribosomal RNA Chemical group 0.000 description 1
- AHYFYQKMYMKPKD-UHFFFAOYSA-N 3-ethoxysilylpropan-1-amine Chemical compound CCO[SiH2]CCCN AHYFYQKMYMKPKD-UHFFFAOYSA-N 0.000 description 1
- UCTWMZQNUQWSLP-UHFFFAOYSA-N Adrenaline Natural products CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 1
- 206010059199 Anterior chamber cleavage syndrome Diseases 0.000 description 1
- 208000010059 Axenfeld-Rieger syndrome Diseases 0.000 description 1
- 101100329226 Bacillus anthracis cpfC1 gene Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101800001415 Bri23 peptide Proteins 0.000 description 1
- 102400000107 C-terminal peptide Human genes 0.000 description 1
- 101800000655 C-terminal peptide Proteins 0.000 description 1
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 101100447432 Danio rerio gapdh-2 gene Proteins 0.000 description 1
- 108700019764 Drosophila oc Proteins 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101150112014 Gapdh gene Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 102000003693 Hedgehog Proteins Human genes 0.000 description 1
- 108090000031 Hedgehog Proteins Proteins 0.000 description 1
- 102000001420 Homeobox domains Human genes 0.000 description 1
- 108050009606 Homeobox domains Proteins 0.000 description 1
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
- 101001082142 Homo sapiens Pentraxin-related protein PTX3 Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000015592 Involuntary movements Diseases 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101150041192 Otx1 gene Proteins 0.000 description 1
- 108700025763 PTX3 Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- BFHAYPLBUQVNNJ-UHFFFAOYSA-N Pectenotoxin 3 Natural products OC1C(C)CCOC1(O)C1OC2C=CC(C)=CC(C)CC(C)(O3)CCC3C(O3)(O4)CCC3(C=O)CC4C(O3)C(=O)CC3(C)C(O)C(O3)CCC3(O3)CCCC3C(C)C(=O)OC2C1 BFHAYPLBUQVNNJ-UHFFFAOYSA-N 0.000 description 1
- 102100036088 Pituitary homeobox 3 Human genes 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 101000606117 Rattus norvegicus Tyrosine 3-monooxygenase Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- FJWGYAHXMCUOOM-QHOUIDNNSA-N [(2s,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6s)-4,5-dinitrooxy-2-(nitrooxymethyl)-6-[(2r,3r,4s,5r,6s)-4,5,6-trinitrooxy-2-(nitrooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-3,5-dinitrooxy-6-(nitrooxymethyl)oxan-4-yl] nitrate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O)O[C@H]1[C@@H]([C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@@H](CO[N+]([O-])=O)O1)O[N+]([O-])=O)CO[N+](=O)[O-])[C@@H]1[C@@H](CO[N+]([O-])=O)O[C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O FJWGYAHXMCUOOM-QHOUIDNNSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 229940102884 adrenalin Drugs 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000009391 cell specific gene expression Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 210000001653 corpus striatum Anatomy 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000010454 developmental mechanism Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 210000000105 enteric nervous system Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000013115 immunohistochemical detection Methods 0.000 description 1
- 238000010249 in-situ analysis Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000030214 innervation Effects 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000004558 lewy body Anatomy 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 108010000889 neuronal pentraxin Proteins 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000003557 neuropsychological effect Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229940079938 nitrocellulose Drugs 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 108090000629 orphan nuclear receptors Proteins 0.000 description 1
- 102000004164 orphan nuclear receptors Human genes 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000008756 pathogenetic mechanism Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229960000482 pethidine Drugs 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 239000003196 psychodysleptic agent Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000007261 regionalization Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007727 signaling mechanism Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 239000002676 xenobiotic agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
L'invention se rapporte aux domaines neurologique, psychiatrique, neuropathologique et neuropharmacologique, et tout particulièrement aux troubles neurologiques et psychiatriques tels que la maladie de Parkinson et la dyskinésie tardive, et aux troubles psychiatriques tels que la schizophrénie, la toxicomanie et les troubles affectifs, du type maladie affective bipolaire, et autres troubles associés au dysfonctionnement du système mésencéphalique dopaminergique (mesDA). L'invention se rapporte à un acide nucléique isolé et/ou recombiné ou à un fragment spécifique, homologue ou dérivé de cet acide nucléique, correspondant à un gène ayant une expression réduite dans les neurones mésencéphaliques dopaminergiques. Le gène en question est lié aux troubles neurologiques et psychiatriques du type maladie de Parkinson, dyskinésie tardive, maladie affective bipolaire et schizophrénie.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97203511.7 | 1997-11-11 | ||
EP97203511 | 1997-11-11 | ||
PCT/NL1998/000652 WO1999024572A1 (fr) | 1997-11-11 | 1998-11-11 | Genes a expression reduite dans les neurones mesencephaliques dopaminergiques |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2309383A1 true CA2309383A1 (fr) | 1999-05-20 |
Family
ID=8228917
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002309383A Abandoned CA2309383A1 (fr) | 1997-11-11 | 1998-11-11 | Genes a expression reduite dans les neurones mesencephaliques dopaminergiques |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1029051A1 (fr) |
AU (1) | AU1179699A (fr) |
CA (1) | CA2309383A1 (fr) |
WO (1) | WO1999024572A1 (fr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007047699A1 (fr) * | 2005-10-17 | 2007-04-26 | Epigenomics Ag | Méthode et acides nucléiques pour le traitement amélioré de cancers du sein |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5229500A (en) * | 1989-08-30 | 1993-07-20 | Regeneron Pharmaceuticals, Inc. | Brain derived neurotrophic factor |
-
1998
- 1998-11-11 CA CA002309383A patent/CA2309383A1/fr not_active Abandoned
- 1998-11-11 WO PCT/NL1998/000652 patent/WO1999024572A1/fr not_active Application Discontinuation
- 1998-11-11 AU AU11796/99A patent/AU1179699A/en not_active Abandoned
- 1998-11-11 EP EP98954850A patent/EP1029051A1/fr not_active Withdrawn
Also Published As
Publication number | Publication date |
---|---|
EP1029051A1 (fr) | 2000-08-23 |
AU1179699A (en) | 1999-05-31 |
WO1999024572A1 (fr) | 1999-05-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8178298B2 (en) | Patched polypeptides and uses related thereto | |
US9868782B2 (en) | DRG11-responsive (DRAGON) gene family | |
AU691469B2 (en) | DNA encoding taurine and gaba transporters and uses thereof | |
JPH09503913A (ja) | ヒト代謝向性グルタミン酸受容体サブタイプ(hmr4,hmr6,hmr7)および関連dna化合物 | |
US6103466A (en) | Double-muscling in mammals | |
US7465552B2 (en) | Patched genes and uses related thereto | |
JP2001509378A (ja) | 哺乳動物におけるダブルマスル化を引き起こすミオスタチン遺伝子の変異 | |
AU672768B2 (en) | DNA encoding a human 5-HT-1E receptor and uses thereof | |
US6946257B1 (en) | Patched genes and uses related thereto | |
JPH10510143A (ja) | Alk−7(アクチビン様キナーゼ)、セリンスレオニンキナーゼレセプター | |
US6589787B2 (en) | T-type calcium channel variants; compositions thereof; and uses | |
KR20050042826A (ko) | 쥐피알54 넉-아웃 포유류 및 이를 이용한 스크리닝 방법 | |
JP2006511194A (ja) | テネウリンc末端関連ペプチド(tcap)並びにこれらに関連する方法および使用 | |
CA2309383A1 (fr) | Genes a expression reduite dans les neurones mesencephaliques dopaminergiques | |
US7446239B2 (en) | SCA2 knockout animal and methods of use | |
JP2001501469A (ja) | 腫瘍抑制タンパク質をコードする核酸分子およびその単離方法 | |
US6518400B1 (en) | Polynucleotide encoding a protein involved in chromosomal inheritance and method of use therefor | |
WO2003004528A1 (fr) | Recepteurs couples a la proteine g humaine et leurs utilisations | |
US6239258B1 (en) | Human Nkx-2.2 polypeptide-encoding nucleotide sequences | |
DE60024862T2 (de) | "insulinabhängiges sequenz dna bindendes protein-1" (irsdbp-1), dafür kodierendes gen und ihre verwendungen | |
CA2562881A1 (fr) | Nouveaux gpr103 de singe et qrfp de singe et procede d'evaluation d'un compose en utilisant le gpr103 | |
WO1998017793A1 (fr) | Proteines 'fringe' et signalisation de notch | |
WO2003048196A2 (fr) | Moyens et procedes permettant de diagnostiquer et de traiter des malformations cranio-faciales | |
Hong | Identification of new winged helix protein family genes, Mf1 and Hfh1, defective in mouse congential hydrocephalus (ch) and satin (sa) mutants | |
US20040005571A1 (en) | Axs gene and protein and methods related thereto |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FZDE | Discontinued |