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WO2000024776A1 - Nouveau recepteur du type toll et gene de ce recepteur - Google Patents

Nouveau recepteur du type toll et gene de ce recepteur Download PDF

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Publication number
WO2000024776A1
WO2000024776A1 PCT/JP1999/005917 JP9905917W WO0024776A1 WO 2000024776 A1 WO2000024776 A1 WO 2000024776A1 JP 9905917 W JP9905917 W JP 9905917W WO 0024776 A1 WO0024776 A1 WO 0024776A1
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tlr6
toll
amino acid
receptor
mouse
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Japanese (ja)
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Science And Technology Corporation Japan
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Japan Science and Technology Agency
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Japan Science and Technology Corp
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    • 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

Definitions

  • the early stages of the immune response to infection require the production of inflammatory cytodynamics from antigen-presenting cells such as macrophages, which induces a specific response by lymphocytes. . However, little is known about the molecular mechanism of this early reaction.
  • the Drosophila Toll gene is known to be involved in the development of the dorsal-ventral axis during development and in the immune response to bacteria and fungi in adults.
  • the Toll gene product is a type I receptor pig and, when combined with the ligand spaetzle, ultimately induces the production of antibacterial and antifungal substances in adults. Its intracellular signaling pathways have also been investigated in detail.
  • Drosophila Toll activates Pelle, a type of serine reonin kinase, through a tube, an adapter molecule, resulting in transcription of the Rel family. Escapes repression by Dorsal i Cactus with homology to the factor, translocates to the nucleus, and induces transcription.
  • the intracellular region of the Toll gene is widely conserved from plants to vertebrates. In mammals, the intracellular region of the IL-11 receptor family is known to have homology. ing.
  • the signaling mechanism from the IL-11 receptor family is the adapter molecule My D88, and the receptor for serine leonin kinase, IL-1
  • the repression of Ic ⁇ is released via the body-associated kinase (IL-1 Receptor-associated kinase (IRAK)), which activates the rel (Rel) family transcription factor NF- ⁇ .
  • IRAK body-associated kinase
  • This is in contrast to the signal transmission of the Drosophila 'Toll' gene and is thought to be evolutionarily conserved (O'Neill LA, et al., J Leukoc Biol. 1998 63 (6): 650 -657.).
  • Toll-related molecules in humans have been identified. It is a once-transmembrane type I receptor. Like the Drosophila Toll gene, the extracellular domain is a leucine repeat repeat, and the intracellular domain is an IL-1 receptor phage. There is a region homologous to the plant. Toll-related molecules in humans have so far been cloned into five families (TLR1-5) (Rock FL, et al., Proc Natl Acad Sci US A. 1998 95 (2): 588-593.).
  • TLR 4 (hToll) has been the most analyzed among them, and it is possible to express activated TLR4 (hToll) in human T cell line Jurkat cells.
  • NF- / cB is activated to induce the production of inflammatory cytokines such as IL-11, IL-6, and IL-8 (Medzhitov R, et Al., Mol Cell. 1998 2 (2) Medzhitov R, et al., Nature. 1997 388 (6640): 394-397.).
  • monocytes the expression of TLR4 gene is induced in response to lipopolysaccharide (LPS) (Muzio M, et al., J Exp Med. 1998 187 (12): 2097- 2101.). Therefore, it is thought that this molecule is involved in the production of inflammatory cytokines at the early stage of the immune response and the induction of so-called adaptive immunity by specific lymphocytes.
  • LPS lipopolysaccharide
  • Tol 1 molecule may form a larger family, elucidate the mechanism of the responding immune system, and investigate various immune system illnesses and the effects of ⁇ disease infection. To establish toxins and other treatments and preventive measures, Toll There is a demand for elucidation of the whole family. Disclosure of the invention
  • the present inventors have attempted to identify a new molecule belonging to this family, and provide a new molecular species that is considered to belong to the Tol (Tol 1) family.
  • the present invention provides TLR6, a novel molecular species of tolfamily related to a transcription factor NF- ⁇ that regulates the expression of various genes involved in an immune response, and a gene encoding the same. I do.
  • the present invention provides an amino acid sequence represented by SEQ ID NO: 2 or 4 in the Sequence Listing or one or more amino acids in the amino acid sequence are deleted and substituted with another amino acid, And / or a toll-like receptor (TLR6) having an amino acid sequence to which one or more other amino acids have been added.
  • TLR6 toll-like receptor
  • the present invention also relates to a protein having a toll-like receptor (TLR6) action.
  • the present invention also relates to a gene having a nucleotide sequence encoding the novel receptor or protein. More specifically, the present invention relates to a gene having a base acid sequence represented by SEQ ID NO: 1 or 3. BRIEF DESCRIPTION OF THE FIGURES
  • FIG. 1 shows the nucleotide sequence and amino acid sequence (one letter code) of human TLR6 of the present invention.
  • FIG. 2 shows the nucleotide sequence and amino acid sequence (one-letter code) of mouse TLR6 of the present invention.
  • FIG. 3 shows a comparison of amino acid sequences in the intracellular region of the human Toll family.
  • FIG. 4 is a photograph in place of a drawing showing the result of Northern blot analysis of mouse TLR6 in each mouse organ. The lower part of the figure shows the RNA content due to /?-Actin.
  • FIG. 5 shows the results of the TLR6 dual luciferase reporter assay of the present invention.
  • the upper row shows the case of 293 cells, and the lower row shows the case of NIH 3T3 cells.
  • FIG. 1 shows the nucleotide sequence and the amino acid sequence (one-letter code).
  • the nucleotide sequence of the obtained human TLR6 is shown in SEQ ID NO: 1 in the sequence listing.
  • the amino acid sequence is shown in SEQ ID NO: 2 in the sequence listing.
  • FIG. 2 shows the nucleotide sequence and the amino acid sequence (single-letter code).
  • the nucleotide sequence of the obtained mouse TLR6 is shown in SEQ ID NO: 3 in the sequence listing.
  • the amino acid sequence is shown in SEQ ID NO: 4 in the sequence listing.
  • the human TLR6 cDNA has an open reading frame of 2,388 bp, and the expected protein consists of 796 amino acid.
  • the mouse TLR6 cDNA was expected to have an oven reading frame of 2,42 lbp and to consist of 807 amino acids.
  • the homology between the human and the mouse was 77.6% at the DNA level and 73.7% at the amino acid level.
  • TLR6 The amino acid sequence of TLR6 is characteristic of a type I membrane protein. There are hydrophobic sites near the N-terminus and the center, which are thought to correspond to the signal peptide and the ⁇ penetration region, respectively.
  • the To11 family is characterized by an extracellular domain, the leucine litulin repeat domain, and a region homologous to the intracellular IL-1 receptor.
  • Human and mouse TLR6 also have a leucine litulin chili beat domain in the extracellular region, and homology within the cell with the IL_1 receptor family and other To11 families. Having.
  • FIG. 3 shows a comparison of amino acid sequences in the intracellular region of the human To11 family.
  • TLR6 of the present invention has the highest homology to TLR1, with 69.1% amino acid levels between human TLR1 and human TLR6. C. Among them, high homology was shown particularly in the intracellular region.
  • a primer was designed so that about 800 bp of the sequence in the N-terminal region was amplified.
  • the position on the chromosome was determined by the FISH method using the cDNA probe of mouse TLR6. This revealed that mouse TLR6 was present on chromosome 5.
  • TLR6 is thought to be on the same chromosome as TLR1, TLR2, and TLR3 that have been reported to date.
  • TLR6 of the present invention activates NF-B.
  • TLR6 The intracellular region of TLR6 has homology to the IL-1 receptor (IL-1R) family, and may have a similar intracellular signaling pathway. Signals from the IL-1R family cause activation of NF-B. Therefore, it was analyzed whether TLR6 was also involved in the activation of NF-B.
  • IL-1R IL-1 receptor
  • Human wild-type TLR6 was inserted into the expression vector pEF-BOS.
  • a tag was applied to the C-terminus with My c as an epitope (pE F—B ES—My c—T L R 6).
  • the cells were transiently transfected with 0.5, 1.0, and 2.0 ⁇ g of these into 2993 cells and NIH3T3 cells using the Lipofxion method and expressed.
  • 2.0 ⁇ g of wild-type MyD88 pEF-BOS-Flag-MyD88
  • 1.0 ⁇ g of NF—B / reporter plasmid and 0.1 g of pRL—SV40 Vector were simultaneously introduced. Cells were harvested 8 hours after transfection, and the luciferase activity was determined using a dual luciferase reporter assay system (Promega) using a luminometer (Lumminometer). Was measured.
  • FIG. 5 shows the case where 293 cells were flowed, and the lower part Indicates the case where NIH 3 T 3 cells were used.
  • the control of MyD888 showed about a 3-fold increase in luciferase activity in 2993 cells and a about 2-fold increase in luciferase activity in NIH3T3 cells.
  • the group in which TLR6 was expressed no increase in activity was observed in any of the cell types.
  • NF-B could not be activated only by expressing human TLR6 alone, which was the only receptor pig.
  • the human and mouse TLR6 of the present invention have a leucine-rich repeat domain at the N-terminal side, and a cell of the IL-11R family at the C-terminal side following the transmembrane portion. It had homology with the inner domain. It showed the highest homology with TLR1 among TLR-related molecules, TLR families.
  • TLR6 of the present invention Analysis of expression of TLR6 of the present invention by RT-PCR reveals expression in immunocompetent tissues such as thymus and spleen, suggesting a role for this molecule in host defense.
  • TLR6 was thought to transmit a signal to NF- / cB due to its intracellular domain being homologous to the intracellular domain of IL_1R. NF-B could not be activated simply by expressing 293- and NIH3T3 cells. This is because (1) the signal is not transmitted into the cell by the expression of the receptor alone, (2) the signal is transmitted through another pathway, not NF-B, (3) It is conceivable that the response differs depending on the type of cell into which the gene is introduced. In the future, it is necessary to produce active TLR6 and analyze its signaling mechanism.
  • Toll gene product is involved in nonspecific immune responses in the early stage of infection and signaling to adaptive immunity by lymphocytes.
  • the biological response to infection is very important, but in severe infections, too strong a response can cause fatal situations, such as endotoxin. This control of biological response is considered to be very useful clinically.
  • a detailed analysis of the function of the To11 family is expected to help elucidate the molecular mechanism of the initial response to inflammation.
  • Example 1 (cloning of cDNA of mouse TLR6)
  • a homologous search of the EST database using the human TLR1 nucleotide sequence revealed a mouse-derived nucleotide sequence (AA177549) highly homologous to the human TLR1 nucleotide sequence.
  • PCR Polymerase chain reaction
  • PCR was performed using Taq polymerase (Takara Shuzo), 30 cycles of 94 ° C for 30 seconds, 56 ° C for 30 seconds, and 72 ° C for 30 seconds, and one cycle of 72 ° C for 10 minutes. Kuru went.
  • a portion of this PCR product was electrophoresed in agarose gel, stained with ethidium bromide (Nippon Gene), and amplified with approximately 400 bp of cDNA under UV irradiation. It was confirmed. This band was excised from the gel, purified with a wizard (Wizard) (Promega), and then cloned using a TA cleaning kit (Novagen).
  • pT7blue (Novagen) T vector was used as a vector, and the vector and the above DNA were mixed at a molar ratio of 1: 3. DNA was integrated into the vector at.
  • the T vector incorporating DNA was transfected into E. coli DH5, and L containing 100 ⁇ g / ml of Ambicillin (Sigma) and 200 ⁇ g / ml of X-gal (Nacalai Tesque) One broth (L-Broth) I sprayed on a plate of semi-solid medium, about 12 hours 37.
  • the nucleotide sequence of the imported cDNA fragment was determined using a fluorescent sequencer 377 manufactured by Applied Biosystems.
  • the sequencing sam- ble was prepared using PRIMSM, a Ready Reaction Dye Terminator Cycle Sequencing Kit (Available Biosystems).
  • PRIMSM a Ready Reaction Dye Terminator Cycle Sequencing Kit
  • In a microtube add 10 ⁇ 1 of the reaction stock solution, 2.0 ⁇ 1 of 1.6 pmol / ⁇ l of T7 Promoter Primer and 8.0 ⁇ 1 of 0.1 l ⁇ g / ⁇ l. was added and mixed, and 25 cycles of PCR reaction were performed at 96 ° C for 10 seconds, 50 ° C for 5 seconds, and 6 ° C for 4 minutes.
  • the six clones had a nucleotide sequence corresponding to EST (AA177549).
  • a mouse genomic clone containing this sequence was searched in the mouse 129 s V genome library (Stratagene). 1 0 6 corresponding plaques were plates, emerging plaques Nai Ronfiru terpolymer (colony / plaquescreen, NEN Co.) was transferred to, alkali processes Nai b Nfu Iruta has been transferred (1. 5 MN a C 1 , 0.5 minutes on a filter paper impregnated with 0.5 MNaOH, followed by neutralization treatment (1.5 MNaCl, 0.5 MTris-HClH7.5 filter paper impregnated with it).
  • EST (AA177549) fragment probe labeled with 32 P radioisotope was prepared as follows. That is, the EST (AA1774949) fragment was excised from the vector with the restriction enzymes BamHI and SalI and incorporated into an agarose gel. After electrophoresis, the band was stained with ethidium Mubuchi Mide (Nippon Gene Co., Ltd.), and a band of about 400 bp was cut out from the gel under ultraviolet irradiation and purified with a wizard (Promega). The obtained fragment was labeled using a DNA labeling kit (Megaprime DNA labeling kit: Amersyam).
  • the filter prepared by the above method was applied to a SSC solution with a final concentration of 6 times for each component, a Denhardt's solution with a 5 times concentration, 1% SDS, and a boiling water bath with a concentration of 100 g / m1. After immersion in a hybridization solution containing denatured salmon sperm DNA (Sigma) and shaking at 65 ° C for 1 hour, the probe labeled by the method described above was hybridized. The mixture was shaken at 65 ° C. for 18 hours to perform hybridization.
  • the filter is immersed in SSC solution containing 0.1% SDS at a final concentration of 2 times, washed once at 65 ° C, and then added to the final concentration of 0.1% SDS. It was immersed in a 0.2 times concentration SSC solution and washed once at 65 ° C.
  • the washed filter was subjected to autoradiography at 180 ° C using a sensitizing screen. As a result, the strongly exposed clones were picked up, plaques were replated again, and screened twice by the above-mentioned method to completely separate two clones from a single clone.
  • This phage DNA was digested with the restriction enzymes BamHI alone or with BamHI and Sa1I, and similarly with BamHI alone or with BamHI and Sa1I. It has been incorporated into the Smid p Bluscript KS (+).
  • BamHI alone or with BamHI and Sa1I restriction enzymes BamHI alone or with BamHI and Sa1I
  • This sequence was amplified using PCR (Polymerase chain reaction) using the cDNA library of the 17th mouse embryo as a material.
  • the PCR was performed for 30 cycles at 94 ° C. for 30 seconds, 56 ° C. for 30 seconds, 72 ° C. for 30 seconds, and one cycle for 72 ° C. for 10 minutes.
  • the PCR product was subjected to agarose gel electrophoresis and stained. As a result, a band of about 2 kbp was confirmed. This band was cut out of the gel, subjected to TA cloning as described above, and its nucleotide sequence was determined using a sequencer.The nucleotide sequence corresponding to mouse TLR6 in Fig. 2 was obtained. .
  • FIG. 2 shows the nucleotide sequence and the amino acid sequence (one-letter code).
  • the nucleotide sequence of the obtained mouse TLR6 is shown in SEQ ID NO: 3 in the sequence listing.
  • the amino acid sequence is shown in SEQ ID NO: 4 in the sequence listing.
  • Example 2 (cloning of cDNA of human TLR6)
  • a probe for screening human TLR6 was prepared from the nucleotide sequence obtained in Example 1. Specifically, the nucleotide sequence information of mouse TLR6 is changed to ⁇ to synthesize oligonucleotides, 5 '-cctcgagctgagatagagagcatcttg-3' and
  • a partial base sequence of mouse TLR6 was amplified by PCR. This PCR product was similarly TA-cloned, and the nucleotide sequence was determined by sequencing. It was confirmed that a part of the nucleotide sequence of mouse TLR6 was partially amplified. Using this fragment as a probe, a human cDNA clone containing this sequence was searched in the human placenta cDNA library (CLONTECH). A nylon filter was prepared as described above, and a probe of a mouse TLR6 fragment labeled with a radioactive isotope 32 P was prepared. At this time, Xhol and SalI were used as restriction enzymes.
  • the filter prepared by the method described above was applied to a SSC solution with a final concentration of 6 times the concentration of each component, a Denhardt's solution with a concentration of 5 times, 1% SDS, and a boiling water bath of 10 ° g / m1. After immersion in a hybridization solution containing denatured salmon sperm DNA (Sigma) and shaking at 60 ° C for 1 hour, the probe labeled by the above-mentioned method was hybridized. The solution was shaken at 60 ° C. for 20 hours to perform hybridization.
  • the filter is immersed in SSC solution at a final concentration of 2% each containing 0.1% SDS, washed once at 60 ° C, and then further washed with 0.1% SDS.
  • Autoradiography was performed at C. As a result, the strongly exposed clones were picked up, plaques were replated again, and screened twice by the method described above, and 6 clones of a single clone were completely separated.
  • the phage DNA was purified, digested with the restriction enzyme NotI, and incorporated into pBluescriptKs (+) similarly digested with NotI.
  • the DNA sequences of these clones were analyzed by a sequencer, and the DNA sequences shown in FIG. 1 were determined. As described above, the total length of human TLR6 was determined.
  • Fig. 1 shows the nucleotide sequence and amino acid sequence (single-letter code).
  • the nucleotide sequence of the obtained human TLR6 is shown in SEQ ID NO: 1 in the sequence listing.
  • the amino acid sequence is shown in the Sequence Listing. This is shown in array number ⁇ 2.
  • Example 3 Expression of mouse TLR 6 in each tissue
  • Trizol Trizol
  • PCR was performed using Taq polymerase (Takara Shuzo Co., Ltd.), and was carried out for 25 cycles at 94 ° C, 60 ° C for 30 seconds, and 74 ° C for 60 seconds. Cycled. The PCR product was subjected to 1.5% agarose gel electrophoresis, and the amount of amplification was determined by staining. Mouse TLR6 was expressed in thymus, spleen, ovary and lung.
  • Fig. 4 shows the results.
  • Example 4 (Mouse TLR6 chromosomal location)
  • Human wild-type TLR6 was prepared by using PCR with Myc as a shredding tag at the C-terminus. Synthetic oligonucleotides,
  • the expression vector pEF-BOS-Myc-TLR6 constructed in Example 5 was applied to 2933 cells and NIH3T3 cells using the Lipofection method, respectively. , 2.0 g—transiently expressed.
  • wild-type My D 8 8 a (P EF - - BOS F lag -M y D 8 8) 2. was introduced into 0 ⁇ g- excessive resistance.
  • NF—B / reporter plasmid 1.0 ⁇ g
  • the cells were washed with PBS (Phosphate Buffered saline), and then lysed and recovered with a lysis buffer (Lysis Buffer).
  • PBS Phosphate Buffered saline
  • a lysis buffer Lysis Buffer
  • L-II as a substrate for luciferase enzyme and Stop and Glo as an internal control were added, and immediately after that, luciferase activity was measured using a luminometer.
  • the TLR6 of the present invention shows high homology to TLR1 of the TLR family, which is a Toll-related molecule, has a leucine litulin bite domain at the N-terminal side, and has a transmembrane region. Subsequently, the C-terminal side is a novel toll-like (T01-1 ike) receptor having homology to the intracellular domain of IL_1R. It is also clinically important as a substance involved in the signal transmission system in the early stage of the immune response.

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Abstract

L'invention concerne une nouvelle espèce moléculaire TLR6 qui fait partie de la famille Toll apparentée à, par exemple, un facteur de transcription NF-'kappa'B régulant l'expression de différents gènes participant à la réponse immunitaire, ainsi qu'un gène codant ladite espèce. L'invention concerne également un nouveau récepteur du type Toll (TLR6) qui est une molécule apparentée au récepteur Toll, lui-même apparenté à un facteur de transcription NF-'kappa'B régulant l'expression de différents gènes participant à la réponse immunitaire, ainsi qu'un gène codant ledit récepteur.
PCT/JP1999/005917 1998-10-26 1999-10-26 Nouveau recepteur du type toll et gene de ce recepteur Ceased WO2000024776A1 (fr)

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JP10304110A JP2000128900A (ja) 1998-10-26 1998-10-26 新規トル様（Ｔｏｌｌ−ｌｉｋｅ）レセプター及びその遺伝子
JP10/30411019981026 1998-10-26

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Cited By (13)

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Publication number Priority date Publication date Assignee Title
EP1714980A1 (fr) * 2000-05-25 2006-10-25 Schering Corporation Protéines réceptrices humaines, réactifs et méthodes associés
US7230078B2 (en) 2001-09-17 2007-06-12 Nestec S.A. Soluble toll-like receptor
US7271248B2 (en) 1997-05-07 2007-09-18 Schering Corporation Human receptor proteins; related reagents and methods
CN102533775A (zh) * 2012-01-09 2012-07-04 天津师范大学 牙鲆模式识别受体TLR21的cDNA全长序列及其应用
US8546324B2 (en) 2008-09-22 2013-10-01 Cedars-Sinai Medical Center Short-form human MD-2 as a negative regulator of toll-like receptor 4 signaling
US9157914B2 (en) 2006-01-10 2015-10-13 Colgate-Palmolive Company Methods of modulating cell surface receptors to prevent or reduce inflammation
CN105132560A (zh) * 2015-09-11 2015-12-09 天津师范大学 一种采用荧光rt-pcr技术检测牙鲆tlr8基因表达的方法
CN105154532A (zh) * 2015-07-28 2015-12-16 青岛农业大学 一种大菱鲆弧菌和鱼肠道弧菌的双重lamp检测方法
CN105219845A (zh) * 2015-07-28 2016-01-06 青岛农业大学 可同时检测副溶血弧菌和创伤弧菌的双重lamp方法
US20160184426A9 (en) * 2010-07-19 2016-06-30 Yeda Research And Development Co., Ltd. Toll-Like Receptor 4 (Tlr-4) Agonist Peptides For Modulating Tlr-4 Mediated Immune Response
US9512196B2 (en) 2008-09-22 2016-12-06 Cedars-Sinai Medical Center Short-form human MD-2 as a negative regulator of toll-like receptor 4 signaling
US9890202B2 (en) 2010-07-19 2018-02-13 Yeda Research And Development Co. Ltd. Peptides based on the transmembrane domain of a toll-like receptor (TLR) for treatment of TLR-mediated diseases
CN117898258A (zh) * 2022-11-18 2024-04-19 复旦大学附属华山医院 Toll样受体5基因条件过表达动物模型

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Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7271248B2 (en) 1997-05-07 2007-09-18 Schering Corporation Human receptor proteins; related reagents and methods
US7670603B2 (en) 1997-05-07 2010-03-02 Schering Corporation Human DNAX toll-like receptor 4 proteins, related reagents and methods
EP1714980A1 (fr) * 2000-05-25 2006-10-25 Schering Corporation Protéines réceptrices humaines, réactifs et méthodes associés
US7230078B2 (en) 2001-09-17 2007-06-12 Nestec S.A. Soluble toll-like receptor
US9157914B2 (en) 2006-01-10 2015-10-13 Colgate-Palmolive Company Methods of modulating cell surface receptors to prevent or reduce inflammation
US8546324B2 (en) 2008-09-22 2013-10-01 Cedars-Sinai Medical Center Short-form human MD-2 as a negative regulator of toll-like receptor 4 signaling
US9512196B2 (en) 2008-09-22 2016-12-06 Cedars-Sinai Medical Center Short-form human MD-2 as a negative regulator of toll-like receptor 4 signaling
US20160184426A9 (en) * 2010-07-19 2016-06-30 Yeda Research And Development Co., Ltd. Toll-Like Receptor 4 (Tlr-4) Agonist Peptides For Modulating Tlr-4 Mediated Immune Response
US9890202B2 (en) 2010-07-19 2018-02-13 Yeda Research And Development Co. Ltd. Peptides based on the transmembrane domain of a toll-like receptor (TLR) for treatment of TLR-mediated diseases
CN102533775A (zh) * 2012-01-09 2012-07-04 天津师范大学 牙鲆模式识别受体TLR21的cDNA全长序列及其应用
CN102533775B (zh) * 2012-01-09 2014-06-25 天津师范大学 牙鲆模式识别受体TLR21的cDNA全长序列及其应用
CN105219845A (zh) * 2015-07-28 2016-01-06 青岛农业大学 可同时检测副溶血弧菌和创伤弧菌的双重lamp方法
CN105154532A (zh) * 2015-07-28 2015-12-16 青岛农业大学 一种大菱鲆弧菌和鱼肠道弧菌的双重lamp检测方法
CN105154532B (zh) * 2015-07-28 2018-10-30 青岛农业大学 一种大菱鲆弧菌和鱼肠道弧菌的双重lamp检测方法
CN105219845B (zh) * 2015-07-28 2018-10-30 青岛农业大学 可同时检测副溶血弧菌和创伤弧菌的双重lamp方法
CN105132560A (zh) * 2015-09-11 2015-12-09 天津师范大学 一种采用荧光rt-pcr技术检测牙鲆tlr8基因表达的方法
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