CN107233579A - The application of IL 12p40 (/) IL 2R α (/) mouse model - Google Patents

The application of IL 12p40 (/) IL 2R α (/) mouse model Download PDF

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CN107233579A
CN107233579A CN201710537321.9A CN201710537321A CN107233579A CN 107233579 A CN107233579 A CN 107233579A CN 201710537321 A CN201710537321 A CN 201710537321A CN 107233579 A CN107233579 A CN 107233579A
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mouse
cell
marrow
myelofibrosis
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廉哲雄
姚远
李亮
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South China University of Technology SCUT
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    • A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
    • A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure

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Abstract

The present invention discloses a kind of application of IL 12p40 (/) IL 2R α (/) mouse model, belongs to medical biotechnology field.Compared with control mice IL 12p40 (/) IL 2R α (+/) mouse, IL 12p40 (/) IL 2R α (/) mouse occurs in that the exception of hemopoietic system, including red blood cell and number of white blood cells are reduced in peripheral blood；CD4 in marrow+T cell and CD8+T cell largely infiltrates, LSK cells (Lin‑c‑Kit+Sca‑1+Cell) ratio and number rise, marrow hemopoiesis ability declines, and a large amount of reticular fibres occurs in marrow；There is extramedullary hematopoiesis in splenomegaly, spleen and liver.Therefore, IL 12p40 (/) IL 2R α (/) mouse can be used to screen treatment LADA myelofibrosis medicine as a kind of animal model.

Description

The application of IL-12p40 (-/-) IL-2R α (-/-) mouse model
Technical field
The invention belongs to medical biotechnology field, a kind of IL-12p40 (-/-) IL-2R α (-/-) are concretely related to Application of the mouse model in the medicine of screening treatment LADA myelofibrosis.
Background technology
Myelofibrosis (Myelofibrosis) is a kind of disease of hematopoietic system, is mainly in the elderly, is mainly characterized by bone Reticular fibre hyperblastosis in marrow, be usually expressed as candidate stem cell abnormal increase, myeloid cell hyperplasia, anaemia, spleen enlargement, Extramedullary hematopoiesis, survival rate decline of spleen and liver etc..In most cases, myelofibrosis patient with JAK2, CALR, , there is myeloid cell tumour in the gene mutations such as MPL.The pathogenesis of myelofibrosis is considered as caused by mainly gene mutation The fibroblast that is triggered such as the disorder of candidate stem cell differentiation function, megacaryocyte abnormal activation activate and produce a large amount of glue It is former.
But a small number of myelofibrosis patients are accompanied by autoimmunity disease, such as systemic loupus erythematosus, dry syndrome, class wind Wet arthritis, primary biliary cholangitis etc..This LADA myelofibrosis often without JAK2, CALR, The gene mutations such as MPL, it may appear that infiltration of the lymphocyte in marrow, can be treated by immunodepressant corticosteroid. But the research at present for LADA myelofibrosis is also seldom, the tool of unclear LADA myelofibrosis Body pathogenesis.Therefore need suitable animal model to carry out medicament research and development, but lack spontaneous autoimmune bone at present The animal model of marrow fibrosis.
IL-2R α (-/-) mouse is due to shortage IL-2R alpha molecules, development and the function of regulatory T cells are affected, Therefore IL-2R α (-/-) mouse has serious systemic autoimmune diseases, show as spleen and lymph node to become big, T cell outstanding It is CD8+[Willerford, D.M., the et al. such as T cell increases, the rising of Serum Antibody content, spontaneous colitis (1995).Immunity3(4):521-530].Work before finds that IL-2R α (-/-) mouse has Portal inflammation and bile duct Destruction, and the content rise of a variety of inflammatory cytokines in anti-mitochondrial antibody (AMA), serum, table can be detected in serum Bright IL-2R α (-/-) mouse has these symptoms for being similar to the biliar cholangitis of human primary, therefore can be as primary Animal model [Wakabayashi, K., et al. (2006) .Hepatology44 (5) of the biliar cholangitis of property:1240- 1249].The colitis of IL-2R α (-/-) mouse is main by CD4+T cell causes, and autoimmune cholangitis is main by CD8+ T cell causes [Hsu, W., et al. (2009) .Hepatology49 (1):133-140].But IL-2R α (-/-) mouse Autoimmune cholangitis is not very serious, and Portal inflammation and the level that bile duct is destroyed are relatively low, are also not evolved to liver fiber The degree of change.And IL-2R α (-/-) mouse has colitis simultaneously, and colitis is generally not present in human primary's courage In juice cholangitis patient.Therefore we, which hybridize, has obtained IL-12p40 (-/-) IL-2R α (-/-) mouse, the mouse and IL-2R α (-/-) mouse is compared, and the degree of colitis is relatively low, and the degree for the level that Portal inflammation is destroyed with bile duct is higher, occurs in that liver is fine Dimensionization, shows that IL-12p40 (-/-) IL-2R α (-/-) mouse has more serious autoimmune cholangitis [Yao, Y., et al.,(2014).J Autoimmun 51:99-108]。
Myelofibrosis animal model such as JAK2 beforeV617FMouse [Marty, C., et al., (2010) .Blood116 (5):783-7]、GATA1lowMouse [Vannucchi, A.M., et al., (2002) .Blood 100 (4):1123-32]、 MybbooMouse [Papathanasiou, P., et al., (2010) .Blood 116 (26):5849-58] etc., people can be simulated A variety of symptoms of class myelofibrosis.But still lack the animal model of LADA myelofibrosis.
The content of the invention
In order to overcome the shortcoming and deficiency of prior art, it is an object of the invention to provide a kind of IL-12p40 (-/-) IL- 2R α (-/-) application of the mouse model in the medicine of screening treatment LADA myelofibrosis.
IL-12p40 (-/-) IL-2R α (-/-) model mice has a variety of similar human autoimmune's property myelofibrosises Feature.
The purpose of the present invention is achieved through the following technical solutions：
The present invention provides a kind of IL-12p40 (-/-) IL-2R α (-/-) mouse model and treats LADA bone in screening Application in the medicine of marrow fibrosis.
The present invention provides a kind of IL-12p40 (-/-) IL- cultivated as LADA myelofibrosis animal model The method of 2R α (-/-) mouse, comprises the steps：
(1) IL-2R α (+/-) mouse and IL-12p40 (-/-) mouse is hybridized, cultivation obtains IL-12p40 (+/-) IL-2R α (+/-) mouse；
(2) step (1) is cultivated into obtained IL-12p40 (+/-) IL-2R α (+/-) mouse and IL-12p40 (-/-) mouse Hybridized, cultivation obtains IL-12p40 (-/-) IL-2R α (+/-) mouse；
(3) step (2) is cultivated to obtained IL-12p40 (-/-) IL-2R α (+/-) mouse and carries out selfing cultivation, is identified To IL-12p40 (-/-) IL-2R α (-/-) mouse.
IL-2R α (-/-) mouse (B6.129S4-Il2ratm1Dw) wherein used in step (1) and IL-12p40 (-/-) Mouse (B6.129S1-Il12btm1Jm) is purchased from U.S. Jackson laboratories.
The method of wherein identification mouse IL-12p40 genes is whether there is with methods of genotyping identification mice progeny IL-12p40 wild type gene；The method of identification mouse IL-2R α genes is to use CD4 sun in Flow cytometry peripheral blood The CD25 of property cell average fluorescent strength.The CD4 positive cells of IL-2R α (-/-) mouse do not include the positive cells of CD25； And the CD25 of IL-2R α (+/-) mouse CD4 positive cells average fluorescent strength is the half of IL-2R α (+/-) mouse, accordingly The IL-2R α genes of mouse can be identified.
IL-12p40 (-/-) IL-2R α (-/-) mouse obtained the invention further relates to the breeding method by the present invention, enters The experiment of one step proves that the mouse may be used as LADA myelofibrosis model to screen treatment LADA marrow The medicine of fibrosis.
It is observed that compared with control mice IL-12p40 (-/-) IL-2R α (+/-) mouse in the present invention, IL-12p40 (-/-) IL-2R α (-/-) mouse peripheral blood in the number of red blood cell and leucocyte substantially reduce, the content of hemoglobin and red Cell pack is remarkably decreased.There are hematopoietic colonies in the spleen of part IL-12p40 (-/-) IL-2R α (-/-) mouse, and HE dyeing is aobvious Show that Splenic structure changes and substantial amounts of megacaryocyte occurs, the spleen of IL-12p40 (-/-) IL-2R α (-/-) mouse It is middle substantial amounts of LSK (Lin occur-c-Kit+Sca-1+) cell, these results show that IL-12p40 (-/-) IL-2R α (-/-) are small The spleen of mouse occurs in that extramedullary hematopoiesis.Hematopoiesis island is occurred in that in the liver of IL-12p40 (-/-) IL-2R α (-/-) mouse simultaneously, Occur substantial amounts of LSK cells in liver, it was demonstrated that liver equally occurs in that extramedullary hematopoiesis.
The femur and shin bone color of (-/-) IL-2R α (-/-) mouse are partially white we have found that IL-12p40 in the present invention, HE dyes The result of color and reticular fibre silver staining shows that the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse occurs in that fibrosis.Simultaneously B cell, mean constant of red blood cell decline in the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse, show to produce B cell, red blood cell Hematopoiesis function decline.In the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse the ratio and number of LSK cells it is notable on Rise, but bone marrow chimerism experiment proves that the marrow hemopoiesis ability of IL-12p40 (-/-) IL-2R α (-/-) mouse is weaker.
We have found that compared with control mice in the present invention, in the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse CD4+T cell and CD8+The number of T cell significantly increases, and is more likely to effector memory phenotypes, can express more High-caliber IFN-γ.And CD4 in the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse+T cell and CD8+T cell Ratio and marrow in the ratios of LSK cells be proportionate.These results have pointed out the T cell of activation to result in IL-12p40 (-/-) IL-2R α (-/-) mouse hematopoiesis function it is abnormal.
The hemopoietic system of (-/-) IL-2R α (-/-) mouse is abnormal present invention discover that IL-12p40.By detection, Wo Menfa Existing IL-12p40 (-/-) IL-2R α (-/-) mouse can preferably simulate the symptom of human autoimmune's property myelofibrosis.
The present invention has the following advantages and effect relative to prior art：
(1) animal model of myelofibrosis can not spontaneous autoimmune disease at present, it is difficult to simulate the autoimmunity of the mankind Property myelofibrosis.IL-12p40 (-/-) IL-2R α (-/-) mouse has spontaneous generation anaemia, myelofibrosis, marrow T thin The features such as born of the same parents' infiltration, extramedullary hematopoiesis.Therefore, IL-12p40 (-/-) IL-2R α (-/-) mouse can as one it is suitable itself The animal model of immunity myelofibrosis.
(2) IL-12p40 is a kind of critically important cell factor in immune system, can influence CD4+T and CD8+T is thin The function of born of the same parents and differentiation；IL-2R α are the α chains of IL-2 acceptors, for maintaining the balance of immune system to play key effect.We Hybridization obtains the mouse of the double defects of IL-12p40 and IL-2R α, i.e. IL-12p40 (-/-) IL-2R α (-/-) mouse.We have found that Compared with control mice IL-12p40 (-/-) IL-2R α (+/-) mouse, IL-12p40 (-/-) IL-2R α (-/-) mouse occurs in that The exception of hemopoietic system, including red blood cell and number of white blood cells are reduced in peripheral blood；CD4 in marrow+T cell and CD8+T cell A large amount of infiltrations, LSK cells (Lin-c-Kit+Sca-1+Cell) ratio and number rise, marrow hemopoiesis ability declines, and marrow goes out Existing a large amount of reticular fibres；There is extramedullary hematopoiesis in splenomegaly, spleen and liver.Therefore, the mouse can be used as a kind of animal model For screening treatment LADA myelofibrosis medicine.
Brief description of the drawings
It is normal with the blood of IL-12p40 (-/-) IL-2R α (-/-) mouse that Fig. 1 is IL-12p40 (-/-) IL-2R α (+/-) mouse Advise data, including peripheral red blood cells number (RBC), content of hemoglobin (HGB), packed cell volume (HCT), leukocyte count And platelet count (PLT) (WBC).
Fig. 2 is the spleen and the extramedullary hematopoiesis situation of liver of IL-12p40 (-/-) IL-2R α (-/-) mouse；Wherein, A is The spleen photo of part IL-12p40 (-/-) IL-2R α (-/-) mouse, shows hematopoietic colonies；B is IL-12p40 (-/-) IL- The spleen HE of 2R α (+/-) mouse and IL-12p40 (-/-) IL-2R α (-/-) mouse is dyed, IL-12p40 (-/-) IL-2R α (-/-) Splenic structure of mouse changes, and arrow points to megacaryocyte；C is IL-12p40 (-/-) IL-2R α (-/-) mouse Liver HE dyeing, arrow point to hematopoiesis island (hematopoietic islands).
The spleen that Fig. 3 is IL-12p40 (-/-) IL-2R α (+/-) mouse with IL-12p40 (-/-) IL-2R α (-/-) mouse With the LSK cell numbers of liver.
Fig. 4 is the myelofibrosis of IL-12p40 (-/-) IL-2R α (-/-) mouse；Wherein, A is IL-12p40 (-/-) IL-2R α (+/-) mouse and IL-12p40 (-/-) IL-2R α (-/-) femur of mouse and the outward appearance of shin bone are contrasted；B is IL- The marrow HE of 12p40 (-/-) IL-2R α (+/-) mouse and IL-12p40 (-/-) IL-2R α (-/-) mouse is dyed, it can be seen that It there is fibroblast in the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse, and IL-12p40 (-/-) IL-2R α The marrow of (+/-) mouse is then without this phenomenon；C is IL-12p40 (-/-) IL-2R α (+/-) mouse and IL-12p40 (-/-) The marrow reticular fibre silver staining of IL-2R α (-/-) mouse, it can be seen that the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse In there is the reticular fibre of black, and the marrow of IL-12p40 (-/-) IL-2R α (+/-) mouse is then without this phenomenon.
Fig. 5 is that the hemopoietic function of bone marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse is abnormal；Wherein, A is IL-12p40 (-/-) IL-2R α (+/-) mouse and IL-12p40 (-/-) IL-2R α (-/-) mouse marrow in various cell subsets number, Red blood cell, the number of B cell are reduced in the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse；B is IL-12p40 (-/-) The ratio and number of LSK cells in the marrow of IL-2R α (+/-) mouse and IL-12p40 (-/-) IL-2R α (-/-) mouse, as a result Prove that the ratio and number of LSK cells in the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse significantly rise；C is marrow Chimeric experiment is to verify the bone of IL-12p40 (-/-) IL-2R α (+/-) mouse and IL-12p40 (-/-) IL-2R α (-/-) mouse Marrow hematopoietic potential, as a result proves that the marrow hemopoiesis ability of IL-12p40 (-/-) IL-2R α (-/-) mouse is remarkably decreased.
Fig. 6 is the marrow T cell infiltration of IL-12p40 (-/-) IL-2R α (-/-) mouse；Wherein, A is IL-12p40 (-/-) IL-2R α (+/-) mouse and IL-12p40 (-/-) IL-2R α (-/-) mouse marrow in T cell number, as a result show The marrow CD4 of IL-12p40 (-/-) IL-2R α (-/-) mouse+T cell and CD8+The number of T cell significantly rises；B is T cell phenotype in the marrow of IL-12p40 (-/-) IL-2R α (+/-) mouse and IL-12p40 (-/-) IL-2R α (-/-) mouse, As a result the marrow CD4 of IL-12p40 (-/-) IL-2R α (-/-) mouse is shown+T cell and CD8+Effector in T cell Memory ratio is higher, can produce higher levels of IFN-γ；C is the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse LSK cell proportions and marrow CD4+T cell and CD8+The correlation analysis of T cell ratio, as a result proves into positive correlation.
Embodiment
With reference to embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited In this.
It should be appreciated by those skilled in the art that if not otherwise specified, chemical reagent used is equal in following embodiments For the reagent of the commercially available pure rank of analysis.Following zooperies are carried out in accordance with experimental animal ethics.
IL-12p40 (-/-) IL-2R α (-/-) mouse model patent " 201410020633.9, cultivate and be used as liver fiber Change the method with the IL-12p40 of PBC animal model (-/-) IL-2R α (-/-) mouse " disclosed in.
The foundation of embodiment 1.IL-12p40 (-/-) IL-2R α (-/-) mouse
C57BL/6J backgrounds IL-2R α (-/-) mouse (B6.129S4-Il2ratm1Dw) [Willerford, D.M., etal.(1995).Immunity 3(4):521-530] and IL-12p40 (-/-) mouse (B6.129S1-Il12btm1Jm) [Magram,J.,et al.(1996).Immunity 4(5):471-481] it is purchased from U.S. Jackson laboratories (The Jackson Laboratory, maine state of U.S.A, http://www.jax.org/), raise in without special pathogen (SPF) ring In border.
We are hybridized IL-2R α (+/-) mouse and IL-12p40 (-/-) mouse, obtain IL-12p40 (+/-) IL- 2R α (+/-) mouse；Hybridized again with IL-12p40 (-/-) mouse, obtain IL-12p40 (-/-) IL-2R α (+/-) mouse. IL-12p40 (-/-) IL-2R α (-/-) mouse used in experiment and IL-12p40 (-/-) IL-2R α (+/-) mouse is by IL- 12p40 (-/-) IL-2R α (+/-) mouse is bred.Because IL-12p40 and IL-2R α mutator is all comprising a neo Gene, so the method for identification mouse IL-12p40 genes is the method identification IL-12p40 with Genotyping (genotyping) Wild type gene, identify mouse IL-2R α genes method CD4 positive cells in Flow cytometry peripheral blood CD25 average fluorescent strength.The CD4 positive cells of wherein IL-2R α (-/-) mouse do not include the positive cells of CD25；And IL- The CD25 of 2R α (+/-) mouse CD4 positive cells average fluorescent strength is the half of IL-2R α (+/-) mouse, it is possible thereby to reflect Determine mouse IL-2R α genes.All mouse are all used to test in 11 to 13 week old, and experiment meets animal welfare requirement.
The blood routine of embodiment 2. is detected
The peripheral blood of mouse is collected into anticoagulant tube, 150 μ L blood is drawn, blood is collected by Automatic Blood Cell Analyzer Routine data.
As a result Fig. 1 is seen, compared with IL-12p40 (-/-) IL-2R α (+/-) mouse, IL-12p40 (-/-) IL-2R α (-/-) Peripheral red blood cells number (RBC), content of hemoglobin (HGB), packed cell volume (HCT) and the leukocyte count (WBC) of mouse are It is remarkably decreased, but platelet count (PLT) does not have significant change.
The Histopathological examination of embodiment 3.
The liver, spleen and myeloid tissue of mouse are fixed in 4% neutral formalin 1~2 day.Myeloid tissue is placed into 24 hours in decalcifying Fluid (acetic acid of 5% hydrochloric acid+5%).Tissue is cut into 4 μm of thin slice through being dehydrated and being embedded among paraffin.Thin slice H＆E dyeing is carried out after dewaxing.Myeloid tissue shows fibrosis by reticular fibre silver staining.
As a result see Fig. 2, Fig. 3, from Fig. 2 HE colored graphs it can be seen that with IL-12p40 (-/-) IL-2R α (+/-) mouse Compare, the Splenic structure of IL-12p40 (-/-) IL-2R α (-/-) mouse changes, the differentiation of red pulp, white pulp is not obvious enough, And occur in that substantial amounts of megacaryocyte.The liver of IL-12p40 (-/-) IL-2R α (-/-) mouse has hematopoiesis island.These As a result the extramedullary hematopoiesis phenomenon in the spleen and liver of IL-12p40 (-/-) IL-2R α (-/-) mouse is demonstrated.Fig. 3 HE dyes Show that fibroblast, reticular fibre silver staining display occurs in the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse in chromatic graph Obvious reticular fibre can be occurred by going out the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse.
The separation of each cells of organs of embodiment 4. and flow cytometry
Liver is taken out, is ground with the PBS containing 0.2%BSA, 1500rpm centrifuges 5min after steel wire net filtration, and it is heavy to take Form sediment.It is resuspended and is precipitated with 40%Percoll (GE Healthcare companies), 2000rpm centrifugation 20min takes precipitation.Spleen uses two Block slide is ground with PBS/0.2%BSA, through nylon net filter.Femur and shin bone are taken, is drawn and is blown and beaten after PBS with syringe Marrow, through nylon net filter.Collected cell handled through erythrocyte cracked liquid after by hemacytometer under the microscope Carry out cell count.Take 1 × 106Cell, is closed with purifying CD16/32 antibody (Biolegend companies), is then marked anti- CD3、B220、Ter119、Gr-1、NK1.1、CD11c、CD11b(Lineage markers)、c-Kit、Sca-1、CD4、CD8β、 CD62L, CD44 (Biolegend companies), CD8 α (BD companies) fluorescence antibody.For cell factor intracellular dyeing, cell by RPMI-1640 culture mediums containing 10% hyclone are resuspended, with the cytositimulation cocktail containing Protein transport inhibitor (being purchased from eBioscience companies) is stimulated, and 37 DEG C are cultivated 4 hours.Cell is closed with purifying CD16/32 antibody, then It is marked with AntiCD3 McAb, CD4, CD8 β, NK1.1 fluorescence antibody (Biolegend companies), then uses fixer (Biolegend companies) is fixed.Cell after fixation wear film with wearing film liquid (Biolegend companies), then with anti- The fluorescence antibody (Biolegend companies) of IFN-γ is marked.
As a result Fig. 3, Fig. 5, Fig. 6 are seen.Fig. 3 is shown in the spleen and liver of IL-12p40 (-/-) IL-2R α (-/-) mouse LSK cytosises.Fig. 5 shows that prematurity is red thin in each cell subset of marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse The number of born of the same parents, mature erythrocyte and B cell decline, but the number of monocyte and neutrophil leucocyte is not significantly changed, and is shown Red blood cell, the generation of B cell are weakened.Fig. 6 shows CD4 in IL-12p40 (-/-) IL-2R α (-/-) mouse bone marrow cells+T cell And CD8+The number of T cell increases, and CD4+T cell and CD8+The ratio of responsiveness memory T cell rises in T cell, production The ability enhancing of raw IFN-γ；And CD4 in IL-12p40 (-/-) IL-2R α (-/-) mouse bone marrow cells+T cell and CD8+T is thin The ratio of born of the same parents and the ratio of marrow LSK cells point out T cell infiltration in marrow to result in marrow exception into positive correlation.
The bone marrow chimerism of embodiment 6. is tested
Ly5.1/Ly5.2 mouse are irradiated with 10Gy, sterile separation Ly5.2IL-12p40 after 24h (-/-) IL-2R α (+/-) The full bone marrow cell of mouse and Ly5.1IL-12p40 (-/-) IL-2R α (-/-) mouse, takes 5 × 10 respectively5Mixing with cells is transferred Give Ly5.1/Ly5.2 mouse.Recipient mice is detected after 8 weeks.
As a result Fig. 5 is seen.Fig. 5 shows that bone marrow chimerism experiment proves that the marrow of IL-12p40 (-/-) IL-2R α (-/-) mouse is made Blood ability is remarkably decreased.
Above-described embodiment is preferably embodiment, but embodiments of the present invention are not by above-described embodiment of the invention Limitation, other any Spirit Essences without departing from the present invention and the change made under principle, modification, replacement, combine, simplification, Equivalent substitute mode is should be, is included within protection scope of the present invention.

Claims (1)

1.IL-12p40 (-/-) IL-2R α (-/-) mouse model is in the medicine of screening treatment LADA myelofibrosis Application.
CN201710537321.9A 2017-07-04 2017-07-04 The application of IL 12p40 (/) IL 2R α (/) mouse model Pending CN107233579A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
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CN114287390A (en) * 2021-12-30 2022-04-08 南方医科大学南方医院 Method for establishing mouse autoimmune myelofibrosis model

Citations (1)

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Publication number Priority date Publication date Assignee Title
CN103749388A (en) * 2014-01-16 2014-04-30 中国科学技术大学 Method for breeding IL-12p40 (-/-) IL-2R alpha (-/-) mice used as hepatic fibrosis and primary biliary cirrhosis animal models

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
CN103749388A (en) * 2014-01-16 2014-04-30 中国科学技术大学 Method for breeding IL-12p40 (-/-) IL-2R alpha (-/-) mice used as hepatic fibrosis and primary biliary cirrhosis animal models

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Title
JEN C. WANG等: ""Immune Derangements in Patients with Myelofibrosis: The Role of Treg, Th17, and sIL2Rα"", 《PLOS ONE》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114287390A (en) * 2021-12-30 2022-04-08 南方医科大学南方医院 Method for establishing mouse autoimmune myelofibrosis model
CN114287390B (en) * 2021-12-30 2023-02-03 南方医科大学南方医院 Method for establishing mouse autoimmune myelofibrosis model

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