CN115044590B - Application of p53 gene mutant and protein expressed by same in preparation of medicines for diagnosing and treating hypertrophic cardiomyopathy - Google Patents
Application of p53 gene mutant and protein expressed by same in preparation of medicines for diagnosing and treating hypertrophic cardiomyopathy Download PDFInfo
- Publication number
- CN115044590B CN115044590B CN202210771636.0A CN202210771636A CN115044590B CN 115044590 B CN115044590 B CN 115044590B CN 202210771636 A CN202210771636 A CN 202210771636A CN 115044590 B CN115044590 B CN 115044590B
- Authority
- CN
- China
- Prior art keywords
- pro
- leu
- ser
- application
- glu
- 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.)
- Active
Links
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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4746—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used p53
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The application discloses an application of a p53 gene mutant and an expressed protein thereof in preparing a medicine for diagnosing and treating hypertrophic cardiomyopathy, and belongs to the technical field of biology. The application is found through experiments: carrying p53 was observed by echocardiography N236S The left back wall and the interval of the left chamber of the mutated mouse heart are thickened, and the length ratio of the isolated heart to the tibia is increased, so that the p53 gene mutated mouse heart has a cardiac hypertrophy phenotype; the application discloses a new function of p53 gene mutation in regulating and controlling onset of hypertrophic cardiomyopathy for the first time, and the discovery provides a new thought and research direction for the effect of the mutation p53 in the onset process of hypertrophic cardiomyopathy, a new action target point for the treatment of hypertrophic cardiomyopathy and a new strategy for the treatment of hypertrophic cardiomyopathy.
Description
Technical Field
The application relates to the field of biotechnology, in particular to a p53 gene mutant and application of protein expressed by the same in preparation of medicines for diagnosing and treating hypertrophic cardiomyopathy.
Background
Hypertrophic cardiomyopathy (hypertrophic cardiomyopathy, HCM) is a cardiomyopathy characterized by cardiac hypertrophy, and is basically characterized by a high incidence of cardiac hypertrophy and sudden death, and clinically includes primary HCM and acquired HCM. Primary HCM is one of the main causes of sudden death in teenagers and athletes, and is commonly found in young patients between 10 and 35 years of age. Primary HCM is an autosomal dominant genetic disease, about 60% of which can detect distinct pathogenic gene mutations, and it has been found that 27 pathogenic genes encoding thick myofilaments, thin myofilaments, Z disc structural proteins or calcium regulatory related proteins are associated with HCM, but unfortunately, the pathogenesis of HCM caused by gene mutations is still unknown, and about 30% of which is myocardial hypertrophy of unknown origin.
To date, the therapeutic principles of HCM aim to improve symptoms, reduce complications and prevent sudden death. The treatment method mainly comprises the steps of relieving outflow obstruction, improving ventricular compliance, preventing and treating thromboembolic events and identifying high-risk sudden death patients. These treatments, while capable of alleviating the symptoms of the patient to some extent, do not provide a radical cure for HCM. The deep research of HCM pathogenesis provides theoretical basis and scheme guidance for further treatment, namely, the action mechanism of HCM pathogenesis is clear and has important significance for radical treatment of HCM.
Disclosure of Invention
The application aims to provide an application of a p53 gene mutant and an expressed protein thereof in preparing medicines for diagnosing and treating hypertrophic cardiomyopathy, so as to solve the problems in the prior art and provide a novel strategy for HCM treatment and screening of HCM treatment targets and medicines.
In order to achieve the above object, the present application provides the following solutions:
the application provides application of a p53 gene mutant in preparing a medicament for diagnosing and treating hypertrophic cardiomyopathy, wherein the nucleotide sequence of the p53 gene mutant is shown in SEQ ID NO:1 is shown as follows:
atgactgccatggaggagtcacagtcggatatcagcctcgagctccctctgagccaggagacattttcag gcttatggaaactacttcctccagaagatatcctgccatcacctcactgcatggacgatctgttgctgccccaggatgttgaggagttttttgaaggcccaagtgaagccctccgagtgtcaggagctcctgcagcacaggaccctgtcacc gagacccctgggccagtggcccctgccccagccactccatggcccctgtcatcttttgtcccttctcaaaaaacttaccagggcaactatggcttccacctgggcttcctgcagtctgggacagccaagtctgttatgtgcacgtactctcctc ccctcaataagctattctgccagctggcgaagacgtgccctgtgcagttgtgggtcagcgccacacctccagctgggagccgtgtccgcgccatggccatctacaagaagtcacagcacatgacggaggtcgtgagacgctgccccca ccatgagcgctgctccgatggtgatggcctggctcctccccagcatcttatccgggtggaaggaaatttgtatcccgagtatctggaagacaggcagacttttcgccacagcgtggtggtaccttatgagccacccgaggccggctctga gtataccaccatccactacaagtacatgtgtagtagctcctgcatggggggcatgaaccgccgacctatccttaccatcatcacactggaagactccagtgggaaccttctgggacgggacagctttgaggttcgtgtttgtgcctgccctg ggagagaccgccgtacagaagaagaaaatttccgcaaaaaggaagtcctttgccctgaactgcccccagggagcgcaaagagagcgctgcccacctgcacaagcgcctctcccccgcaaaagaaaaaaccacttgatggagagtat ttcaccctcaagatccgcgggcgtaaacgcttcgagatgttccgggagctgaatgaggccttagagttaaaggatgcccatgctacagaggagtctggagacagcagggctcactccagctacctgaagaccaagaagggccagtcta cttcccgccataaaaaaacaatggtcaagaaagtggggcctgactcagactga。
the application also provides application of the protein expressed by the p53 gene mutant in preparing medicaments for diagnosing and treating hypertrophic cardiomyopathy, wherein the amino acid sequence of the protein is shown as SEQ ID NO:2 is shown as follows:
Met Thr Ala Met Glu Glu Ser Gln Ser Asp Ile Ser Leu Glu Leu ProLeu Ser Gln Glu Thr Phe Ser Gly Leu Trp Lys Leu Leu Pro Pro GluAsp Ile Leu Pro Ser Pro His Cys Met Asp Asp Leu Leu Leu Pro GlnAsp Val Glu Glu Phe Phe Glu Gly Pro Ser Glu Ala Leu Arg Val SerGly Ala Pro Ala Ala Gln Asp Pro Val Thr Glu Thr Pro Gly Pro ValAla Pro Ala Pro Ala Thr Pro Trp Pro Leu Ser Ser Phe Val Pro SerGln Lys Thr Tyr Gln Gly Asn Tyr Gly Phe His Leu Gly Phe Leu GlnSer Gly Thr Ala Lys Ser Val Met Cys Thr Tyr Ser Pro Pro Leu AsnLys Leu Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp ValSer Ala Thr Pro Pro Ala Gly Ser Arg Val Arg Ala Met Ala Ile TyrLys Lys Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His HisGlu Arg Cys Ser Asp Gly Asp Gly Leu Ala Pro Pro Gln His Leu IleArg Val Glu Gly Asn Leu Tyr Pro Glu Tyr Leu Glu Asp Arg Gln ThrPhe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Ala Gly SerGlu Tyr Thr Thr Ile His Tyr Lys Tyr Met Cys Ser Ser Ser Cys MetGly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu AspSer Ser Gly Asn Leu Leu Gly Arg Asp Ser Phe Glu Val Arg Val CysAla Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Phe Arg LysLys Glu Val Leu Cys Pro Glu Leu Pro Pro Gly Ser Ala Lys Arg AlaLeu Pro Thr Cys Thr Ser Ala Ser Pro Pro Gln Lys Lys Lys Pro LeuAsp Gly Glu Tyr Phe Thr Leu Lys Ile Arg Gly Arg Lys Arg Phe GluMet Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp Ala His AlaThr Glu Glu Ser Gly Asp Ser Arg Ala His Ser Ser Tyr Leu Lys ThrLys Lys Gly Gln Ser Thr Ser Arg His Lys Lys Thr Met Val Lys LysVal Gly Pro Asp Ser Asp。
the application also provides application of the mouse model transferred into the p53 gene mutant in preparing medicines for screening diagnosis and treatment of HCM.
The application discloses the following technical effects:
the application selects the WT and the p53 of the same age S/S Mice, whose hearts were observed in vivo using cardiac ultrasound, found p53 compared to WT mice S/S The back wall of the left chamber and the space between the chambers of the heart of the mouse are thickened; further observations also found p53 S/S The heart of the mice increased and the ratio of heart to tibia length (HW/TL) increased significantly, indicating p53 S/S Mice developed an HCM phenotype. The application disclosesThe discovery of the p53 gene mutation promotes the new function of HCM occurrence and development, provides a new thought and research direction for research of the pathogenesis of HCM by the p53 gene mutation, provides a new action target for HCM treatment, and provides a new strategy for HCM treatment.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 shows p53 in mice S/S A genotype identification result schematic diagram; m: DNA750bp standard; WT is a wild-type mouse; p53 +/S Is heterozygous mutant mice; p53 S/S Is homozygous mutant mice;
FIG. 2 is p53 S/S A cardiac hypertrophy-related phenotype of the mouse heart; a is WT mouse and p53 S/S Left ventricular wall thickness (LVPWT) data statistics graph measured by heart color Doppler ultrasound of mouse, B is WT mouse and p53 S/S Statistical graph of room space thickness (IVST) data measured by heart color Doppler ultrasound of mice, C being WT mice and p53 S/S Statistical plot of the mice heart-to-tibia length ratio (HW/TL).
Detailed Description
Various exemplary embodiments of the application will now be described in detail, which should not be considered as limiting the application, but rather as more detailed descriptions of certain aspects, features and embodiments of the application.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. In addition, for numerical ranges in this disclosure, it is understood that each intermediate value between the upper and lower limits of the ranges is also specifically disclosed. Every smaller range between any stated value or stated range, and any other stated value or intermediate value within the stated range, is also encompassed within the application. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application. All documents mentioned in this specification are incorporated by reference for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the application described herein without departing from the scope or spirit of the application. Other embodiments will be apparent to those skilled in the art from consideration of the specification of the present application. The specification and examples of the present application are exemplary only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are intended to be inclusive and mean an inclusion, but not limited to.
The p53 gene mutation of the present application refers to p53 N236S (in humans p 53) N239S Hereinafter referred to as p53 S/S) 。
Example 1p53 S/S Mouse genotyping
1. Mouse propagation
To get more p53 S/S Mouse (p 53) S/S The mouse model construction method refers to "Gain of function in the mouse model of a recurrent mutation p53 (N236S) promotes the formation of double minute chromosomes and the oncogenic potential of p (ARF)") and we select p53 for use S/S (♂)×p53 S/+ Hybridization; the male and female mice were placed together in the afternoon (typically 2-4 month old mice), and the female mice were observed for vaginal suppositories before 9 hours the next morning, if vaginal suppositories were to be kept separately, and the production was awaited. The mice are born for 21-30 days, and the mice are pressedThe sex is divided into cages, the ear tags are used for numbering, and the tail tip tissues are taken for genotyping.
2. DNA extraction from mouse tail tip tissue
(1) Placing the tissue of the mouse tail tip into a 1.5mL centrifuge tube, and numbering the centrifuge tube corresponding to the ear mark of the mouse;
(2) Adding 500 μl of tail lysate and 10 μl of proteinase K, mixing with vortex mixer, and reacting at 55deg.C overnight;
(3) Adding 500 μl of Tris saturated phenol the next day, mixing with vortex mixer, centrifuging at 13000rpm at 4deg.C for 10 min;
(4) After the centrifugation, layering phenomenon can be observed, taking supernatant, adding equal volume of isopropanol, mixing uniformly, and centrifuging at 13000rpm and 4 ℃ for 15 minutes;
(5) The supernatant was discarded, 800. Mu.l of 70% ethanol was added thereto, and the mixture was centrifuged at 13000rpm at 4℃for 10 minutes;
(6) The supernatant was discarded, inverted and dried, and then approximately 50. Mu.l of sterilized water was added for dissolution, followed by centrifugation to obtain DNA.
In order to eliminate the influence of hormone level, the application selects male p53 S/S Mice were subjected to subsequent experiments.
3. PCR genotyping
3.1 The PCR primer sequences were as follows:
p53 S/S -F：5’-ctgcaccctacgagaactgactt-3’；(SEQ ID NO：3)；
p53 S/S -R：5’-gggatgaagtgatgggagctag-3’；(SEQ ID NO：4)
p53 S/S -F3：5’-gcataagcttggatccgttcttcggac-3’；(SEQ ID NO：5)
3.2 PCR reaction system
p53 S/S Genotyping PCR reaction system:
TABLE 1 PCR reaction System
3.3 PCR reaction conditions
p53 S/S Genotyping PCR (polymerase chain reaction) assayThe following conditions are adopted:
TABLE 2 PCR reaction conditions
3.4 detection of PCR products by agarose gel electrophoresis
Agarose gel electrophoresis: after the PCR reaction, adding 4 μl of 6×loading Buffer, mixing, adding the PCR reaction product into 2% agarose gel, 120V,200mA,30min; genotype determination based on the running gel fruits (see fig. 1): p53 wild type (p 53) +/+ ) The amplified band of the allele of (2) is 458bp; heterozygote (p 53) S/+ After Neo removal) amplified bands were: 294bp, 458bp and 634 bp; homozygous mutant (p 53) S/S After Neo removal) allele bands were: 294bp, 634bp.
Example 2 characterization of cardiac hypertrophy phenotype in mice
1. Echocardiography in vivo observation of mouse hearts
1.1 preparation of WT and p53 with a week of 8-12 weeks of age S/S Male mice, matched in age, were injected intraperitoneally with anesthetic and allowed to enter a general anesthesia state.
1.2 using a small animal ultrasonic probe, connecting an ultrasonic signal collector, observing the beating condition of a mouse heart, and respectively measuring the left ventricular rear wall thickness (LVPWT) and the ventricular septum thickness (IVST) of the mouse heart, wherein the results show that: p53 S/S LVPWT, IVST of the mouse heart thickened significantly more than WT mouse heart, the above changes indicate p53 S/S The mouse heart developed a hypertrophic ultrasound phenotype.
2. Observation of the isolated form of the mouse heart
(1) Preparation of WT and p53 with a week of 8-12 weeks of age S/S Male mice are matched with each other in age, anesthetic is injected into the abdominal cavity, and the mice are sacrificed after neck breakage after entering an anesthetic state.
(2) Alcohol kills the mouse fur, cuts the chest skin, cuts the rib on the left side of the sternum, opens the chest, exposes the heart, and cuts the aorta along the aortic root, and the heart is isolated.
(3) The isolated hearts were placed in a petri dish containing Phosphate Buffered Saline (PBS), the blood cells in the chamber were washed, the liquid was blotted dry with absorbent paper, and the heart weight was weighed using an electronic balance.
(4) The two hind limbs are taken, the tibia is separated, the muscles attached to the tibia are peeled off cleanly, the length of the tibia on both sides is measured by a ruler, and the average value is taken.
(5) The HW/TL ratio was obtained using the average of the length of the tibia over the heart weight ratio of the mice. The ratio is an important index for judging myocardial hypertrophy, and our results show that: p53 S/S The HW/TL ratio of the mice was significantly higher than that of the WT mice.
The above experiments show that: the application discloses the cardiac hypertrophy phenotype of the heart of the mutant p53 mouse for the first time; the discovery provides a new thought and a new direction for mutation p53 in research of HCM pathogenesis, provides a new biomarker for HCM clinical screening and diagnosis, and also provides a new strategy for HCM treatment.
The above embodiments are only illustrative of the preferred embodiments of the present application and are not intended to limit the scope of the present application, and various modifications and improvements made by those skilled in the art to the technical solutions of the present application should fall within the protection scope defined by the claims of the present application without departing from the design spirit of the present application.
Sequence listing
<110> university of Kunming engineering
<120> p53 gene mutant and application of protein expressed by same in preparation of medicines for diagnosing and treating hypertrophic cardiomyopathy
<160> 5
<170> SIPOSequenceListing 1.0
<210> 1
<211> 1173
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 1
atgactgcca tggaggagtc acagtcggat atcagcctcg agctccctct gagccaggag 60
acattttcag gcttatggaa actacttcct ccagaagata tcctgccatc acctcactgc 120
atggacgatc tgttgctgcc ccaggatgtt gaggagtttt ttgaaggccc aagtgaagcc 180
ctccgagtgt caggagctcc tgcagcacag gaccctgtca ccgagacccc tgggccagtg 240
gcccctgccc cagccactcc atggcccctg tcatcttttg tcccttctca aaaaacttac 300
cagggcaact atggcttcca cctgggcttc ctgcagtctg ggacagccaa gtctgttatg 360
tgcacgtact ctcctcccct caataagcta ttctgccagc tggcgaagac gtgccctgtg 420
cagttgtggg tcagcgccac acctccagct gggagccgtg tccgcgccat ggccatctac 480
aagaagtcac agcacatgac ggaggtcgtg agacgctgcc cccaccatga gcgctgctcc 540
gatggtgatg gcctggctcc tccccagcat cttatccggg tggaaggaaa tttgtatccc 600
gagtatctgg aagacaggca gacttttcgc cacagcgtgg tggtacctta tgagccaccc 660
gaggccggct ctgagtatac caccatccac tacaagtaca tgtgtagtag ctcctgcatg 720
gggggcatga accgccgacc tatccttacc atcatcacac tggaagactc cagtgggaac 780
cttctgggac gggacagctt tgaggttcgt gtttgtgcct gccctgggag agaccgccgt 840
acagaagaag aaaatttccg caaaaaggaa gtcctttgcc ctgaactgcc cccagggagc 900
gcaaagagag cgctgcccac ctgcacaagc gcctctcccc cgcaaaagaa aaaaccactt 960
gatggagagt atttcaccct caagatccgc gggcgtaaac gcttcgagat gttccgggag 1020
ctgaatgagg ccttagagtt aaaggatgcc catgctacag aggagtctgg agacagcagg 1080
gctcactcca gctacctgaa gaccaagaag ggccagtcta cttcccgcca taaaaaaaca 1140
atggtcaaga aagtggggcc tgactcagac tga 1173
<210> 2
<211> 390
<212> PRT
<213> Artificial sequence (Artificial Sequence)
<400> 2
Met Thr Ala Met Glu Glu Ser Gln Ser Asp Ile Ser Leu Glu Leu Pro
1 5 10 15
Leu Ser Gln Glu Thr Phe Ser Gly Leu Trp Lys Leu Leu Pro Pro Glu
20 25 30
Asp Ile Leu Pro Ser Pro His Cys Met Asp Asp Leu Leu Leu Pro Gln
35 40 45
Asp Val Glu Glu Phe Phe Glu Gly Pro Ser Glu Ala Leu Arg Val Ser
50 55 60
Gly Ala Pro Ala Ala Gln Asp Pro Val Thr Glu Thr Pro Gly Pro Val
65 70 75 80
Ala Pro Ala Pro Ala Thr Pro Trp Pro Leu Ser Ser Phe Val Pro Ser
85 90 95
Gln Lys Thr Tyr Gln Gly Asn Tyr Gly Phe His Leu Gly Phe Leu Gln
100 105 110
Ser Gly Thr Ala Lys Ser Val Met Cys Thr Tyr Ser Pro Pro Leu Asn
115 120 125
Lys Leu Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val
130 135 140
Ser Ala Thr Pro Pro Ala Gly Ser Arg Val Arg Ala Met Ala Ile Tyr
145 150 155 160
Lys Lys Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His
165 170 175
Glu Arg Cys Ser Asp Gly Asp Gly Leu Ala Pro Pro Gln His Leu Ile
180 185 190
Arg Val Glu Gly Asn Leu Tyr Pro Glu Tyr Leu Glu Asp Arg Gln Thr
195 200 205
Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Ala Gly Ser
210 215 220
Glu Tyr Thr Thr Ile His Tyr Lys Tyr Met Cys Ser Ser Ser Cys Met
225 230 235 240
Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp
245 250 255
Ser Ser Gly Asn Leu Leu Gly Arg Asp Ser Phe Glu Val Arg Val Cys
260 265 270
Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Phe Arg Lys
275 280 285
Lys Glu Val Leu Cys Pro Glu Leu Pro Pro Gly Ser Ala Lys Arg Ala
290 295 300
Leu Pro Thr Cys Thr Ser Ala Ser Pro Pro Gln Lys Lys Lys Pro Leu
305 310 315 320
Asp Gly Glu Tyr Phe Thr Leu Lys Ile Arg Gly Arg Lys Arg Phe Glu
325 330 335
Met Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp Ala His Ala
340 345 350
Thr Glu Glu Ser Gly Asp Ser Arg Ala His Ser Ser Tyr Leu Lys Thr
355 360 365
Lys Lys Gly Gln Ser Thr Ser Arg His Lys Lys Thr Met Val Lys Lys
370 375 380
Val Gly Pro Asp Ser Asp
385 390
<210> 3
<211> 23
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 3
ctgcacccta cgagaactga ctt 23
<210> 4
<211> 22
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 4
gggatgaagt gatgggagct ag 22
<210> 5
<211> 27
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 5
gcataagctt ggatccgttc ttcggac 27
Claims (1)
1. The application of a mouse model transformed with a p53 gene mutant in screening medicines for treating hypertrophic cardiomyopathy is characterized in that the nucleotide sequence of the p53 gene mutant is shown as SEQ ID NO: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210771636.0A CN115044590B (en) | 2022-06-30 | 2022-06-30 | Application of p53 gene mutant and protein expressed by same in preparation of medicines for diagnosing and treating hypertrophic cardiomyopathy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210771636.0A CN115044590B (en) | 2022-06-30 | 2022-06-30 | Application of p53 gene mutant and protein expressed by same in preparation of medicines for diagnosing and treating hypertrophic cardiomyopathy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115044590A CN115044590A (en) | 2022-09-13 |
| CN115044590B true CN115044590B (en) | 2023-08-15 |
Family
ID=83165427
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210771636.0A Active CN115044590B (en) | 2022-06-30 | 2022-06-30 | Application of p53 gene mutant and protein expressed by same in preparation of medicines for diagnosing and treating hypertrophic cardiomyopathy |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115044590B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115044590B (en) * | 2022-06-30 | 2023-08-15 | 昆明理工大学 | Application of p53 gene mutant and protein expressed by same in preparation of medicines for diagnosing and treating hypertrophic cardiomyopathy |
Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6031088A (en) * | 1996-05-23 | 2000-02-29 | Albert Einstein College Of Medicine Of Yeshiva University | Polycystic kidney disease PKD2 gene and uses thereof |
| CN101805738A (en) * | 2009-11-12 | 2010-08-18 | 昆明理工大学 | Peculiar p53 mutated protein-p53N236S of ALT tumor caused by progeria syndrome and application thereof |
| CN102625837A (en) * | 2009-08-07 | 2012-08-01 | 国立大学法人京都大学 | Method of efficiently establishing induced pluripotent stem cells |
| CN102648287A (en) * | 2009-08-24 | 2012-08-22 | 菲吉尼克斯公司 | Detecting PAX2 for the diagnosis of breast cancer |
| CN107447005A (en) * | 2017-08-15 | 2017-12-08 | 昆明理工大学 | P53 gene mutations and the purposes of telomere dysfunction |
| CN108330167A (en) * | 2017-09-13 | 2018-07-27 | 昆明理工大学 | The new application of p53 gene mutations |
| CN108486248A (en) * | 2018-03-14 | 2018-09-04 | 昆明理工大学 | The purposes of p53 gene mutations in tumour associated fibroblast cell |
| CN112028983A (en) * | 2020-05-25 | 2020-12-04 | 百世诺(北京)医学检验实验室有限公司 | Novel mutant protein related to dilated cardiomyopathy, novel mutant gene and application thereof |
| CN112135632A (en) * | 2018-02-02 | 2020-12-25 | 肿瘤免疫股份有限公司 | Methods of selecting and designing safer and more effective anti-CTLA-4 antibodies for cancer therapy |
| JP2021525281A (en) * | 2018-07-09 | 2021-09-24 | ▲ふぇん▼潮医薬科技（上海）有限公司 | Use of RyR2 protein or RyR2 recombinant protein in the manufacture of anti-heart failure drugs |
| WO2021231474A1 (en) * | 2020-05-12 | 2021-11-18 | Pmv Pharmaceuticals, Inc. | METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION |
| CN113981065A (en) * | 2021-11-02 | 2022-01-28 | 百世诺（北京）医疗科技有限公司 | Hypertrophic cardiomyopathy pathogenic gene MYBPC3 with c.223dupG heterozygosis missense and application thereof |
| CN114107312A (en) * | 2021-11-12 | 2022-03-01 | 江苏百世诺医疗科技有限公司 | Mutant hypertrophic cardiomyopathy pathogenic gene MYBPC3 and application thereof |
| CN114921543A (en) * | 2022-06-20 | 2022-08-19 | 昆明理工大学 | Application of p53 mutant gene in screening of drugs for promoting wound repair |
| CN115044590A (en) * | 2022-06-30 | 2022-09-13 | 昆明理工大学 | Application of p53 gene mutant and protein expressed by same in preparation of medicine for diagnosing and treating hypertrophic cardiomyopathy |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8043801B2 (en) * | 2007-11-23 | 2011-10-25 | Jeanne Y. Wei | Method of screening for agents to treat heart failure |
| US20130079382A1 (en) * | 2009-10-12 | 2013-03-28 | Larry J. Smith | Methods and Compositions for Modulating Gene Expression Using Oligonucleotide Based Drugs Administered in vivo or in vitro |
| WO2013009979A2 (en) * | 2011-07-13 | 2013-01-17 | Smith Holdings, Llc | Compositions and methods for suppressing gene expression of p53 and clusterin |
| WO2016081897A1 (en) * | 2014-11-21 | 2016-05-26 | University of the Sciences of Philadelphia | COMPOSITIONS AND METHODS OF USING THERAPEUTIC p53 PEPTIDES AND ANALOGUES |
-
2022
- 2022-06-30 CN CN202210771636.0A patent/CN115044590B/en active Active
Patent Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6031088A (en) * | 1996-05-23 | 2000-02-29 | Albert Einstein College Of Medicine Of Yeshiva University | Polycystic kidney disease PKD2 gene and uses thereof |
| CN102625837A (en) * | 2009-08-07 | 2012-08-01 | 国立大学法人京都大学 | Method of efficiently establishing induced pluripotent stem cells |
| CN102648287A (en) * | 2009-08-24 | 2012-08-22 | 菲吉尼克斯公司 | Detecting PAX2 for the diagnosis of breast cancer |
| CN101805738A (en) * | 2009-11-12 | 2010-08-18 | 昆明理工大学 | Peculiar p53 mutated protein-p53N236S of ALT tumor caused by progeria syndrome and application thereof |
| CN107447005A (en) * | 2017-08-15 | 2017-12-08 | 昆明理工大学 | P53 gene mutations and the purposes of telomere dysfunction |
| CN108330167A (en) * | 2017-09-13 | 2018-07-27 | 昆明理工大学 | The new application of p53 gene mutations |
| CN112135632A (en) * | 2018-02-02 | 2020-12-25 | 肿瘤免疫股份有限公司 | Methods of selecting and designing safer and more effective anti-CTLA-4 antibodies for cancer therapy |
| CN108486248A (en) * | 2018-03-14 | 2018-09-04 | 昆明理工大学 | The purposes of p53 gene mutations in tumour associated fibroblast cell |
| JP2021525281A (en) * | 2018-07-09 | 2021-09-24 | ▲ふぇん▼潮医薬科技（上海）有限公司 | Use of RyR2 protein or RyR2 recombinant protein in the manufacture of anti-heart failure drugs |
| WO2021231474A1 (en) * | 2020-05-12 | 2021-11-18 | Pmv Pharmaceuticals, Inc. | METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION |
| CN112028983A (en) * | 2020-05-25 | 2020-12-04 | 百世诺(北京)医学检验实验室有限公司 | Novel mutant protein related to dilated cardiomyopathy, novel mutant gene and application thereof |
| CN113981065A (en) * | 2021-11-02 | 2022-01-28 | 百世诺（北京）医疗科技有限公司 | Hypertrophic cardiomyopathy pathogenic gene MYBPC3 with c.223dupG heterozygosis missense and application thereof |
| CN114107312A (en) * | 2021-11-12 | 2022-03-01 | 江苏百世诺医疗科技有限公司 | Mutant hypertrophic cardiomyopathy pathogenic gene MYBPC3 and application thereof |
| CN114921543A (en) * | 2022-06-20 | 2022-08-19 | 昆明理工大学 | Application of p53 mutant gene in screening of drugs for promoting wound repair |
| CN115044590A (en) * | 2022-06-30 | 2022-09-13 | 昆明理工大学 | Application of p53 gene mutant and protein expressed by same in preparation of medicine for diagnosing and treating hypertrophic cardiomyopathy |
Non-Patent Citations (1)
| Title |
|---|
| 突变p53功能研究新进展与个性化的肿瘤治疗新策略;陆思千;贾舒婷;罗瑛;;遗传(第06期);第539-548页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115044590A (en) | 2022-09-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zeviani et al. | Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNALeu (UUR) | |
| KR20190100967A (en) | Optimized Strategy for Exon Skipping Modifications with CRISPR / CAS9 with Triple Guide Sequences | |
| JP2015128440A (en) | Novel therapeutical tools and methods for treating blindness | |
| CN101300346B (en) | Novel biological substance nesfatin and its related substances and uses thereof | |
| CN1143372A (en) | Haemopoietic manuration factor | |
| CN115044590B (en) | Application of p53 gene mutant and protein expressed by same in preparation of medicines for diagnosing and treating hypertrophic cardiomyopathy | |
| CN108079317A (en) | Orally active receptor activators treat obesity-related disease method and system | |
| RU2384586C2 (en) | Disease-related protein | |
| CN109295221B (en) | Application of circular RNA as colorectal cancer molecular marker | |
| WO2018028249A1 (en) | Mirna and use thereof in treatment of metabolic disease | |
| CN108707655A (en) | The application of serodiagnosis marker occurs as Japanese schistosomiasis liver fibrosis for β-actin albumen | |
| US20020172959A1 (en) | Compositions and methods relating to lung specific genes and proteins | |
| Mechoulam et al. | Expression and activation of STAT3 in ischemia-induced retinopathy | |
| AU2004291809B2 (en) | Method of growing myocardial cells | |
| US20040166105A1 (en) | Compositions and methods relating to breast specific genes and proteins | |
| CN110184275B (en) | NF1 new mutation pathogenic gene, application and kit | |
| CN114317720B (en) | Application of hsa_circ_0066715 gene and detection method thereof | |
| CN102732607A (en) | Kit for detecting high myopia | |
| CN102051366B (en) | Chicken fat candidate gene lpin1 and functional mutation detection method | |
| CN110592214B (en) | Use of PGM2L1 gene in preparation of marker for diagnosing ovarian cancer, diagnostic reagent and therapeutic drug | |
| Shimizu-Matsumoto et al. | Isolation and chromosomal localization of the human cone cGMP phosphodiesterase γ cDNA (PDE6H) | |
| CN100390286C (en) | Novel enzyme gene and its expression product | |
| KR102108455B1 (en) | Genetic Marker for Diagnosis of Nosema disease and Diagnostic Method of Nosema disease | |
| CN114470214B (en) | Deubiquitinase ZRANB1 function and application for regulating lipid metabolism | |
| CN105283544A (en) | Animal model of Charcot-Marie-Tooth disease as HSP27 mutant (S135F) carrier |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |