CN101288602A - Method for establishing radiation induced vitiligo mice model and application thereof - Google Patents

Method for establishing radiation induced vitiligo mice model and application thereof Download PDF

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CN101288602A
CN101288602A CNA2008100534639A CN200810053463A CN101288602A CN 101288602 A CN101288602 A CN 101288602A CN A2008100534639 A CNA2008100534639 A CN A2008100534639A CN 200810053463 A CN200810053463 A CN 200810053463A CN 101288602 A CN101288602 A CN 101288602A
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vitiligo
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王月英
李德冠
吴红英
孟爱民
路璐
褚丽萍
王彦
张俊伶
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Institute of Radiation Medicine of CAMMS
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Abstract

The invention provides a method for establishing a radiation-induced vitiligo mouse model by applying different doses of Gamma-ray to carry out whole body irradiation of an IRM-2 mouse. The radiation-induced vitiligo mouse model is mainly used for the research of pathogenesis of vitiligo and the development of drugs for prevention and treatment, and can also be used for the research of tumourgenesis immune mechanism and the screening of targets for immunotherapy as well as for the research of radiation-induced immune dysfunction mechanism. The model of the invention is characterized by simple preparation, early lesion emergence time, high incidence, low radiation dose and so on, and further lays the foundation for the experimental research of the pathogenesis of vitiligo and the screening of new drugs at the same time.

Description

Set up the method and the application thereof of radiation induced vitiligo mice model
Technical field
The present invention relates to a kind of method for building up of radiation induced vitiligo mice model, be used for vitiligo Study on Pathogenesis and control drug screening and evaluation; Be used for the screening of tumorigenic immunologic mechanism research and immunization therapy target spot.Be used for radiation-induced immunologic function disorder mechanism or radiation and regulate the research of immunologic function.
Background technology
Vitiligo is a kind of common depigmentation dermatoses, and clinical manifestation is the local skin white macula, in case morbidity, the low and easy delay progress of cure rate causes very big physical and psychological pressure to the patient.Leukodermic pathological change mainly is that the melanocyte that produces dermal melanin sustains damage.Cause destructive cell of patients with vitiligo melanocyte and molecular mechanism not to be illustrated as yet.The cause of disease is very complicated, lacks with the not clear nutrient of biochemical change, neural factor, the disorder of radical protection balancing and melanocyte; Melanocyte sticks defective and inherited genetic factors etc. confidential relation.What obtain at present that the people in the industry generally admits is immunologic mechanism.
Clinical observation finds that vitiligo has often with other autoimmune diseasees, has pointed out leukodermic immunopathogenesis mechanism.Can detect the autoantibody of anti-melanocyte and melanin leach protein thereof in some research prompting patients with vitiligo serum, but more research prompting vitiligo is the autoimmune disease of cellular immunization mediation.The processing of autoantigen and the process of presenting also are not very clear.In multinomial research, be proved, many and the synthesis of melanin proteins associated of melanocyte, as tryrosinase, tyrosinase related protein-1 and-2 (TRP-1 and TRP-2) and melanosome structural protein MART1/Melan-A, Pme117/gp100 and gp75 etc., belong to intracellular protein, by I type MHC at cell surface expression, very likely by antigenic specificity CD8+T cell recognition.Cytotoxic T cell (CTL) may mediate melanocyte death.Regulatory T lymphocyte (Treg) balance disorder in addition, patients with vitiligo the CD4+CD25+ cell occurs and raise, and the imbalance of prompting immunologic tolerance may be one of vitiligo pathogenesis.Biochemical ANOMALOUS VARIATIONS finally also is to change relevant with induction of immunity.Biochemical unusual main two aspects that show of vitiligo: catecholamine and metabolite thereof raise in (1) hematuria; (2) antioxidant system imbalance, high-caliber hydrogen peroxide in the epidermis.High-caliber hydrogen peroxide makes tyrosine and other single phenols generation hydroxylation reactions generate corresponding pyrocatechol, further is oxidized into benzoquinone.Can act on tryrosinase after the long-time accumulation of benzoquinone and make the latter form hapten, thus challenge.
Because the vitiligo pathogenesis is unclear, be easy to diagnosis clinically but treatment difficulty relatively.Set up easy, reliably fall ill model for research leukodermic pathogeny and the treatment target spot have important significance for theories and practical significance.The laboratory animal relevant with vitiligo has at present: (1) Smythline (SL) chicken SL chicken is the leukodermic animal model of mankind itself's immunity, is founded in the seventies in 20th century by the Smyth of State of Massachusetts, US university professor.This model aspect disease pathology many particularly very similar aspect the immunology to human vitiligo.(2) C57BL/6J Ler-vit/vit C57BL mouse hair color is a black.Its subbreed has C57BL/6, C57BL/6J, C57BL/10 etc.More easily bring out immunologic tolerance, mice B16 melanoma cell series originates from the C57BL/6 mice.The C57BL/6JLer-vit/vit mice is the homeotic mutation system of C57BL/6J, is leukodermic mouse model.Professor Lerner by Yale sets up.The range of application of C57BL mouse is wider, the research relevant with vitiligo mainly contains hair follicle melanocyte propagation and the adjusting of differentiation and the research of vitiligo secondary color, antineoplastic immune and anti-tumor biological treatment and leukodermic research of melanoma dependency and the leukodermic heredity of Mus etc.(3) Cavia porcellus outbreeding group Cavia porcellus, but adularescent, yellowish-brown, black etc. divided by its hair color.An amount of functional melanocyte to UVB and PUVA sensitivity is wherein arranged in the yellowish-brown Cavia porcellus epidermis, skin behind ultraviolet radiation can produce apparent hyperpigmentation, in the epidermis dopa-positive melanocytes quantity more not irradiated site increase by 3~4 times, the melanocyte dendron increases.This phenomenon and process are similar to the tanned phenomenon of the pigmentation of human ultraviolet induction, particularly yellow.Therefore, this model is usually used in studying the pigmentation of ultraviolet induction and the psoralen photochemotherapy in the therapy of vitiligo and is used for tyrosinase inhibitor and the pharmacodynamic study of sunscreen; (4) domestic Anhui Chinese Medicine College professor Long Zijiang of chemical decolorization model utilizes chemicals such as hydroquinone or hydrogen peroxide to carry out part decolouring to have prepared Cavia porcellus vitiligo model.
The IRM-2 mice is to hybridize with ICR/JCL mice, 615 mices, by modifying the inbred mouse that single line is cultivated.The IRM-2 mice has stronger toleration to ionizing radiation, and the spontaneous tumor incidence rate is low.But to multiple mouse inoculation tumor cell susceptible, as adenocarcinoma of lung T795, Lewis lung cancer, breast carcinoma TA2, hepatocarcinoma Hep A, leukemia L1210, cervical cancer U14, sarcoma S180, LM lymphatic cancer, B16 melanoma, H22 hepatocarcinoma.Find that in carrying out the radiosensitivity experimentation IRM-2 mice after the radioactive exposure is prone to the hair decolouring.The inventor finds by deep research and a large amount of experiments: IRM-2 mice peripheral blood lymphocyte CD4/CD8 ratio reduces, and changes similar with clinical patients with vitiligo.For this reason, set up suitable vitiligo animal model for inquiring into vitiligo study of pathogenesis and drug development, the inventor has carried out many-sided test at laboratory, observes the generation and the mechanism thereof of IRM-2 mice radioactive exposure induced vitiligo.About the method for building up of IRM-2 mice radioactive exposure induced vitiligo animal model, do not see the report of relevant similar document both at home and abroad so far as yet at present.
Summary of the invention
The present invention is the pure lines IRM-2 mice that utilizes my unit to cultivate, and sets up the mouse model of radiation induced vitiligo, is used for vitiligo Study on Pathogenesis and control drug screening and evaluation; Be used for the screening of tumorigenic immunologic mechanism research and immunization therapy target spot.Be used for radiation-induced immunologic function disorder mechanism or radiation and regulate the research of immunologic function.
For achieving the above object, the invention provides a kind of method of setting up radiation induced vitiligo mice model, may further comprise the steps:
A kind of method of setting up radiation induced vitiligo mice model may further comprise the steps:
(1) selects pure lines IRM-2 mice group, make it under the whole body radiation gamma, trichochromes occur and take off mistake.
(2) observed after the single total irradiation for 10 weeks, preferably write down incidence rate, the time of origin of hair decolouring under the different exposure doses, the order of severity of morbidity.
(3) setting up with radiation-induced IRM-2 mice hair decolouring is the mouse model of feature.
Radiation of the present invention comprises ionizing radiation and Non-ionizing radiation.Ionizing radiation wherein refers to alpha-particle, beta-particle, proton, neutron and X ray, gamma-rays;
Non-ionizing radiation refers to visible light, infrared ray, ultraviolet, electromagnetic radiation etc.
The present invention preferably refers to the 137Cs radiation gamma, exposure dose be 1~6 lattice auspicious (gray, Gy), the single total irradiation.
Selection pure lines IRM-2 mice group of the present invention is meant: the IRM-2 mice is divided into seven groups, and male and female have concurrently, and every group of 7-9 only is divided into 0 (matched group), and 1,2,3,4,5, the 6Gy group.Two kinds of mices that the dosage grouping will be shone same dosage together carry out whole body 137Cs radiation gamma 4-8 week, and the grouping of irradiation back is raised and long-term observation; Regularly observe the skin depigmentation situation, do record.
Radiation-induced IRM-2 mice vitiligo model of the present invention is to adopt aforementioned disclosed method to obtain.
The present invention further discloses radiation-induced IRM-2 mice vitiligo application of model.Comprise: radiation induced vitiligo mice model is used for vitiligo Study on Pathogenesis and control drug screening and evaluation; Be used for the screening of tumorigenic immunologic mechanism research and immunization therapy target spot; Be used for radiation-induced immunologic function disorder mechanism or radiation and regulate the research of immunologic function; Be used for the reference of radiation-induced other autoimmune disease models; Be used for other chemicalses and induce the skin depigmentation model.
Radiation induced vitiligo mice model of the present invention is compared the good effect that is had with existing various vitiligo models and is:
(1) IRM-2 that selects for use of the present invention has be easy to occur the characteristic that trichochromes takes off mistake under total irradiation; Radiation-induced IRM-2 mice vitiligo occurs early, and exposure dose is low, more meets the general functional status of anthropomorphic body; Only need the total irradiation of single gamma-rays can become model, method is easy.Also can expand different schemes and set up model; And can select different exposure doses according to the needs of test.
(2) the IRM-2 MOUSE REPRODUCTION rate height selected for use of the present invention, growth is fast, and resistance is strong, has cheaply as the animal model of radiation induced vitiligo, is easy in research and the characteristics of promoting the use of in using.
(3) the IRM-2 mice vitiligo model of the present invention's foundation provides clue for studying radiation damage immunocyte mechanism and vitiligo pathogeny, and also exploitation and the evaluation for treatment vitiligo medicine provides objective criterion.
(4) model of the present invention have that preparation is simple, the pathological changes time of occurrence early, the incidence rate height, characteristics such as radiation dose is low also are the pathogenetic experimentation of exploitation vitiligo simultaneously, the screening new drug is laid a good foundation.
Experimental result proves: the IRM-2 mice vitiligo model that the present invention set up belongs to the susceptible model.Therefore, induce for chemical toxicant or some immunosuppressant virus to cause the immunocyte damage, the vitiligo that skin pigment takes off mistake has directive significance equally.The IRM-2 mice vitiligo model that adopts the present invention simultaneously and set up also can carry out chemical toxicant or some immunosuppressant virus and induce the pharmacological research that causes immunocyte damage vitiligo medicine and the screening of vitiligo new drug.
The specific embodiment
Now in conjunction with the embodiments, carry out in addition further instruction of description that mechanism inquires into to animal model constructing method of the present invention and as model.
Embodiment 1
Experiment purpose:, inquire into radioactive exposure and induce the IRM-2 mice to set up vitiligo mice model according to laboratory observation in the past.
Experiment material:
1. laboratory animal C57BL/6 mice is available from dimension tonneau China, approval number: SCXK (capital) 2007-0001; The IRM-2 mice is from Chinese medicine research institute institute of radio-medicine, approval number: SCXK (Tianjin): 2005-00019.The IRM-2 mice is to hybridize with ICR/JCL mice, 615 mices, by modifying the inbred mouse that single line is cultivated, sale is arranged externally.ICR/JCL mice wherein, available from Institute of Radiation Medicine, Chinese Academy of Medical Sciences, 615 mices are available from Chinese Academy of Medical Sciences's hematopathy institute.
2. reagent K 3EDTA is available from Sigma; CD4, CD8, CD25, B220, NK1.1 are available from eBioscience company.CD11c and Lysing Buffer are available from BD Pharmingen company.Cell titer-Glo TMTest kit is available from U.S. Promega company; Methylcellulose culture medium (MethoCult
Figure A20081005346300071
GF M3534), StemCell Technologies.Superoxide dismutase (SOD) testing cassete builds up bio-engineering research institute available from Nanjing.
3. experimental apparatus 137Cs radiation gamma source: Atomic Energy of Canada Ltd., the USD type, Autocell 140, close rate 0.79Gy/min.Inverted microscope: optical instrument factory, Chongqing; CoulterAltra flow cytometer: U.S. Beckman; GloMax TMLuminous detection instrument: U.S. Promega.
Experimental technique:
1. experiment grouping and irradiation
This experiment is divided into seven groups with mice, and male and female have concurrently, and every group of 7-9 only.Be divided into matched group, 1,2,3,4,5, the 6Gy group.Two kinds of mices to shining same dosage according to the dosage grouping together carry out total irradiation, shine back grouping raising and long-term observation skin depigmentation situation and carry out record.
2. skin depigmentation is observed and the record method
The skin depigmentation situation is regularly observed in the irradiation back.After decolouring occurring, observe the skin depigmentation situation weekly, and carry out the integration record respectively by two people.Mice hair decolouring standards of grading are: hair did not have decolouring in 0 minute; Hair had decolouring in 1 minute; 2 fens hair decolouring area>10%; 3 fens hair decolouring area>25%; 4 fens hair decolouring area>50%; 5 fens hair decolouring area>75%.
3. pathologic sampling and fixing means
The irradiation back is observed 10w and is drawn materials.Mice is taken a picture to skin lesion after putting to death.
3.1. skin is fixed: use 8%Na 2The depilation of S mice at decolouring and no bleaching intersection, cuts the rectangle skin of the about 1.5cm of width.After taking off skin skin is launched to be attached on the filter paper, neutral formalin is fixed.
3.2. peel off mouse kidney and spleen, after weighing, neutral formalin is fixed.
4. immunological assay method
Mice is won eyeball and gets blood 4.1 draw materials, K 3The EDTA anticoagulant.
4.2. dyeing is got the 50ul anticoagulation and joined in the 1ml hemocyte lysate, behind the concussion mixing, lucifuge is placed 15min.With twice back of the PBS solution washing that contains 1% serum supernatant discarded, add 100ul PBS and hanged cell, add corresponding antibody, behind the mixing, lucifuge is hatched 15min, and middle mixing is once.The PBS that adds 400ul at last, mixing filters, and carries out fluidic cell and detects.Use EXP032 software to detect and analyze with supporting EXP032 Analysis software.
4.3. result treatment adopts SPSS11.0 software to carry out statistical procedures
5. oxidative damage parameters is measured
Mice is won eyeball and gets blood, and preparation serum provides method to measure mice serum superoxide dismutase (SOD) determination of activity by producer.
6. the femur nucleated cell is counted
The aseptic mouse femur of getting, the flushing medullary cell, the mixing after-filtration, counting cells, count results is shown with every femur nucleated cell numerical table.
7. colony forms (clone) ability mensuration
Packing methylcellulose culture medium ,-20 ℃ of preservations.With being prepended in the 2-8 ℃ of refrigerator or thawing under the room temperature; Separate bone marrow cells in mice, the blue dyeing counting cell of Placenta Hominis is adjusted cell concentration and is added M3534, and the abundant mixing of agitator leaves standstill and treats bubble collapse, connects 16# tack syringe needle with the 3ml syringe, adds 24 orifice plates and puts into wet box, inserts 37 ℃, 5%CO 2Cultivated 14 days in the incubator.Colony morphological observation and counting.Observe under inverted microscope from cultivating beginning in the 5th day.Low power is observed colony and is formed situation, the positive colony in cell number 〉=30, and colony-forming efficiency is with per 10 5Individual plastidogenetic colony numerical table shows.
Experimental result and discussion:
(1) radiation-induced IRM-2 mice hair decolouring incidence rate:
After 4 weeks of irradiation, IRM-2 male mice irradiation 6Gy group skin pigment all occurs and takes off the change of mistake sexually transmitted disease (STD), and IRM-2 female mice and C57 male mice all occur.After shining for 8 weeks, IRM-2 male mice irradiation 3-6Gy the vitiligo skin pigment all occurs and takes off mistake, and 3Gy group sickness rate is 25%, and 4Gy group sickness rate is 75%, and the 5-6Gy group is 100%.Vitiligo has appearred in IRM-2 female mice irradiation 4-6Gy, and sickness rate is all male consistent with the dose irradiation group with IRM-2.And the C57 male mice only vitiligo occurs at irradiation 5Gy and 6Gy, and 5Gy group sickness rate is 33%, and 6Gy group sickness rate is 100%.The hair decolouring incidence rate of mice is similar to 8 weeks after 10 weeks of irradiation.Above result shows that the skin depigmentation pathological changes can appear in IRM-2 mice acceptance irradiation, compares with matched group C57BL/6 mice, and the dosage of radiation-induced hair decolouring is low, and incidence rate is dose dependent.
The sickness rate of mice after 8 weeks of table 1 irradiation
Figure A20081005346300091
(2) the radiation-induced mice irradiation of various dose back hair decolouring time of occurrence
Observe different exposure dose mices and the earliest time of pathological changes occurs, the results are shown in Table 2.
The result shows that IRM-2 mice pathological changes occurs early.And exposure dose is high more, and the time that the hair decolouring occurs more early.
The radiation-induced mice hair decolouring of table 2 various dose time of occurrence
Figure A20081005346300101
(3) the radiation-induced mice irradiation of various dose back hair decolouring area
After shining for 4 weeks the decolouring of the male 6Gy irradiation of IRM-2 group is only arranged, the decolouring area must be divided into 1.00 ± 0.00.After shining for 8 weeks, various mice decolouring area scores all are dose-dependence.The results are shown in Table 2.IRM-2 mice and C57 mice comparing difference have significance.
The different mices in the table 3 irradiation 8 week back area that on average decolours
Figure A20081005346300102
The different mices in the irradiation 10 week backs area that on average decolours increases, and integration is dose-dependence.The results are shown in Table 4.
The different mices in the table 4 irradiation 10 week back area that on average decolours
Figure A20081005346300103
Above result shows, be easy to occur the skin depigmentation sexually transmitted disease (STD) after the radioactive exposure of IRM-2 mice and become, relatively bring out disease with C57 and decrease the occurrence rate height, the sick damage occurs early, and lesion degree is dose-response relationship, obtains to be similar to the model of application on human skin depigmentation (vitiligo) thus.Therefore, the feature that can utilize radiation-induced IRM-2 mice hair decolouring is used for the exploitation of pathogenetic discussion of vitiligo and control medicine as inductivity vitiligo model.And provide as the probability of inquiring into other autoimmune disease models.
Embodiment 2
Radiation-actuate vitiligo mice amynologic mechanism is inquired into, and experimental design is the same.
1. healthy mice peripheral blood immunocyte typing
Gather the mice peripheral blood and carry out immunocyte typing flow cytometry, the results are shown in Table 4.By detecting CD4, CD8, CD25, D11b, NK1.1, found that IRM-2 mice and C57 mice are compared, CD4 and CD4/CD8 have certain difference, and the CD4/CD8 that shows as the IRM-2 mice is lower than the C57 mice.CD11b then is that the IRM-2 mice is higher than the C57 mice.Two kinds of mices of CD25 and NK1.1 do not see obvious difference.The difference meaning of two kinds of mouse immune cell typings awaits further discussion.
Table 5 healthy mice cell, humoral immunization index
Figure A20081005346300111
2. radioactive exposure mice peripheral blood immunocyte typing
Carry out after the radioactive exposure blood sampling of 10 weeks and carry out T lymphocyte subsets in spleen of mice immunized and observe, find that IRM-2CD4, CD8 raise with exposure dose, downward trend is arranged, CD4/CD8 has rising trend, prompting CD4 damage behind radiation irradiation with CD8 and the degree recovered different.
Mice periphery blood T lymphocyte hypotype after table 6 radioactive exposure
Figure A20081005346300112
Figure A20081005346300121
Testing result finds that radiation causes that exposing mice peripheral blood lymphocyte CD25/CD4 raises, and is dosage dependence trend.Two groups of mices do not see notable difference.The results are shown in Table 7.
Mice peripheral blood CD25 measures after table 7 radioactive exposure
Figure A20081005346300122
Detect mice peripheral blood B cell subgroup, find that irradiation back mice B220 raises than matched group, prompting may be that the T percentage of lymphocyte reduces relatively.Reflection DC and NK cell phenotype are not seen notable difference.The results are shown in Table 8.
Table 8 radiation base reveals back mice peripheral blood immunocyte phenotype to be changed
Figure A20081005346300123
3. radioactive exposure mice hemopoietic immunocyte
As can be seen from Table 8, mouse bone marrow cells nucleated cell counting after 10 weeks of radioactive exposure and peripheral blood leucocyte counting are not seen notable difference (seeing Table 9) with matched group.But the proliferation of bone marrow cells function is suppressed, and is dose dependent.IRM-2 bone marrow cells in mice proliferation activity is higher than contrast C57 mice (P<0.05~0.01), and radiation is lower than C57 mice (the results are shown in Table 10) to the active inhibition degree of bone marrow proliferation.
Mice hemopoietic immunocyte after table 9 radioactive exposure
Figure A20081005346300131
Mouse bone marrow cells CFU-GM after table 10 radioactive exposure
Figure A20081005346300132
Important organ such as thymus, spleen, lung and kidney weight irradiation group mice and control group mice are not seen notable difference.The results are shown in Table 11 and table 12.
Mouse immune organ index after table 11 radioactive exposure
Figure A20081005346300133
Figure A20081005346300141
Mice organ index after table 12 radioactive exposure
Figure A20081005346300142
This experimental selection sublethal dose 1~6Gy irradiation, minute is for being subjected to according to back 10 weeks.From organ weights and bone marrow, peripheral blood leucocyte count results, two groups of mices and irradiation group and matched group do not have significant difference, but the proliferation of bone marrow cells function still is subjected to inhibition in various degree, and IRM-1 medullary cell counting is high, irradiation back suppression ratio is low, and is consistent with its radioresistance characteristic.
The peripheral blood lymphocyte typing found that, compares with the C57 mice, and IRM-2 mice CD/CD8 ratio is higher, and difference has significance.CD25/CD4 is also slightly high.The CD4/CD8 ratio of IRM-2 is rising trend after the total irradiation, and this species diversity may be relevant with some biological characteristics of IRM-2.
The two positive cells of CD25/CD4 are a kind of of regulatory T cells.The mode of regulatory T cells (regulatoryT cells, Treg cell) by " initiatively " suppresses immune system to the replying of self and exotic antigen, and has important effect aspect immunity of organism tolerance and the immunne response stable state keeping.This experiment is found to increase by 1~6Gy with exposure dose, and the CD25/CD4 cell proportion raises, but two kinds of mices do not see obvious difference.After various dose irradiation that this research of these results suggest is selected, through recovering for a long time, though internal organs do not see that variation has appearred in the balance between the obvious damage immunocyte, may be with to cause some autoimmunity sample disease to take place relevant.Set up IRM-2 mice vitiligo model and provide clue, also provide the objective criterion standard for medicine exploitation and evaluation for research radiation damage immunocyte mechanism and vitiligo pathogeny.
Embodiment 3
Radiation-induced skin depigmentation sexually transmitted disease (STD) becomes the discussion of peroxide injury mechanism
IRM-2 mice and C57 mice irradiation 1 week of back, get peripheral blood, preparation serum is measured the SOD vigor, found that not irradiation group IRM-2 is lower than the C57 mice; Irradiation back SOD vigor descends, and 2Gy, 4GyIRM-2 mice reduce about 10%, and the C57 mice reduces by 30%, 40% respectively.Prompting irradiation back IRM-2 SOD in Mice vigor is higher.
CuZn-SOD vigor (U/ml) in table 13 mice serum
Figure A20081005346300151
In sum, among the embodiment that content of the present invention is not confined to, the knowledgeable people in the same area can propose other embodiment easily within technological guidance's thought of the present invention, but this embodiment comprises within the scope of the present invention.

Claims (9)

1, a kind of method of setting up radiation induced vitiligo mice model may further comprise the steps:
(1) selects pure lines IRM-2 mice, make its whole body under radiation gamma, trichochromes occur and take off mistake;
(2) observed after the single total irradiation for 10 weeks, write down incidence rate, the time of origin of hair decolouring under the different exposure doses, the order of severity of morbidity;
(3) setting up with radiation-induced IRM-2 mice hair decolouring is the mouse model of feature.
2, the described method of setting up radiation induced vitiligo mice model of claim 1, IRM-2 mice wherein is to hybridize with ICR/JCL mice, 615 mices, by modifying the inbred mouse that single line is cultivated.
3, the described method of setting up radiation induced vitiligo mice model of claim 1, wherein said radiation comprises ionizing radiation or Non-ionizing radiation.
4, the described method of setting up radiation induced vitiligo mice model of claim 1, single total irradiation wherein refers to 1~6Gy, the total irradiation of 137Cs gamma-rays single.
5, a kind of radiation induced vitiligo mice model is characterized in that being obtained by each described method for building up of claim 1-4.
6, the defined radiation induced vitiligo mice model of a kind of claim 5 is characterized in that vitiligo mice model is used for the application of vitiligo Study on Pathogenesis and drug screening.
7, the defined radiation induced vitiligo mice model of a kind of claim 5 is characterized in that being used for the application of tumorigenic immunologic mechanism and the screening of immunization therapy target drug.
8, the defined radiation induced vitiligo mice model of a kind of claim 5 is characterized in that being used for radiation-induced immunologic function disorder mechanism or the application of immunologic function is regulated in radiation.
9, the defined radiation induced vitiligo mice model of a kind of claim 5 is characterized in that being used for the application of radiation-induced other autoimmune disease models.
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CN103081816A (en) * 2011-11-07 2013-05-08 中国辐射防护研究院 Point source irradiating method and tool for chronic irradiation of animals in batch experiments
RU2566201C1 (en) * 2014-11-24 2015-10-20 Федеральное государственное бюджетное учреждение "Уральский научно-исследовательский институт дерматовенерологии и иммунопатологии Министерства здравоохранения Российской Федерации" (ФГБУ "УрНИИДВиИ" Минздрава России) Method of treating vitiligo
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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103081816A (en) * 2011-11-07 2013-05-08 中国辐射防护研究院 Point source irradiating method and tool for chronic irradiation of animals in batch experiments
RU2566201C1 (en) * 2014-11-24 2015-10-20 Федеральное государственное бюджетное учреждение "Уральский научно-исследовательский институт дерматовенерологии и иммунопатологии Министерства здравоохранения Российской Федерации" (ФГБУ "УрНИИДВиИ" Минздрава России) Method of treating vitiligo
CN111149767A (en) * 2020-02-24 2020-05-15 中南大学湘雅二医院 Humanized skin type lupus erythematosus mouse model and construction method and application thereof
WO2021212653A1 (en) * 2020-04-24 2021-10-28 苏州大学 Method for screening treatment target for acute radiation gastrointestinal syndrome, and application of tigar target in preparation of drug for treating radiation gastrointestinal syndrome
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