Abstract:Objective To evaluate the effect of Osteoking on blood physiological parameters and organ indexes in the ovariectomized tree shrew model of osteoporotic fracture (OPF). Methods A total of 30 4-month-old female tree shrews (Tupaia belangeri) were randomly divided into control group, model group and treatment group, with 10 in each group. Bilateral ovaries of the tree shrews in the treatment group and model group were removed and osteoporosis was confirmed 6 months later. Then tibial fractures were generated. From the next day of fracture, tree shrews in the treatment group were gavaged with Osteoking once every two days, and tree shrews in the model group and control group were gavaged with equal volume of sterile saline. After gavaging for 3 months, 16 blood physiological parameters and 6 organ indexes of the tree shrews in each group were measured. Results Among all of the 16 blood physiological parameters, the number of white blood cells, the absolute value and percentage of lymphocytes (P < 0.01) and monocytes (P < 0.05) in the model group were significantly lower than those in the control group after 3 months. Compared with the model group, the absolute value and percentage of monocytes (P < 0.01) and lymphocytes, the number of white blood cells (P < 0.05) and the spleen coefficient were significantly increased (P < 0.05) in the treatment group. Conclusions Osteoking can improve the immunity of tree shrews with osteoporotic fracture.

Abstract:Objective To determine the hematological and serum biochemical parameters of 50 healthy African green monkeys, and to analyze the difference of these values between different groups of sex and age (the juvenile group:1-3 years old, the adult group:4-6 years old). Methods Blood samples were obtained from the monkeys in the awake state, and the hematological and serum biochemical parameters of the samples were measured using an automatic blood cell analyzer and blood biochemical analyzer, respectively. Results Among all of the hematologic values, the number of red blood cells (RBC), the amount of hemoglobin (HGB), hematocrit (HCT), and percentages of the neutrophils (NEUT%), lymphocytes (LYMPH%), monocytes (MONO%) and basophils (BASO%) were significantly different between the juvenile group and the adult group (P < 0.05). In the juvenile group, parameters such as the number of the white blood cells (WBC), RBC, HGB, HCT, NEUT%, LYMPH%, MONO% were significantly different between the female and the male monkeys (P < 0.05). As for the adult group, the HCT value was of significant difference, while the other indexes were not significantly different between the female and male monkeys (P < 0.05). Among the serum biochemical values, the quantities of albumin (ALB), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and creatinine (CREA) were significantly different between the juvenile group and adult group (P < 0.05). The amount of CREA of the juvenile females was significantly different from that of the juvenile males (P < 0.05), and the values of total protein (TP) and cholesterol (CHOL) of the adult females were significantly different from those of the adult males (P < 0.05), while the other indexes were not significantly different. Conclusions As a reference, the routine biological data of African green monkeys we have established in this study lay a foundation for the evaluation of their biological properties and further application in related studies.

Abstract:Objective To investigate the correlation between cognitive development and levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the hippocampus of 80-day-old neonatal rats born of fear-impaired pregnant rats. Methods The pregnant rat model of fear-impaired kidney was established by watching other rats shocked with electricity. The cognitive development of the neonatal rats was assessed by Morris water maze test at 80 days after birth. The brain microdialysis samples of the right hippocampus were collected using a stereotaxic instrument, and the levels of DA and DOPAC were determined by HPLC-ECD. Results Compared with the control group, the mean escape latency of the 80-day-old neonatal rats in the model group was increased. Their swimming speed was slower. The 20% time spent in the peripheral zone became longer, and the frequency of platform crossing was decreased, showing significant differences (P< 0.05). The levels of DA and DOPAC in the extracellular fluid of the hippocampus of the 80-day-old neonatal rats in the model group were decreased at each time points of perfusion, showing a significant difference (P < 0.05). The level of DA, a kind of monoamine neurotransmitter in the hippocampus, was positively correlated with the mean escape latency, the frequency of passing the platform of the 80-day-old rats, while was negatively correlated with the 20% time spent in the peripheral zone, with a significant correlation (P< 0.05). In addition, there was a positive correlation between the DOPAC level and the mean escape latency, the frequency of passing the platform (P< 0.05). Conclusions Fear-impaired pregnant rats can affect the spatial learning and memory ability of their 80-day-old neonatal rats, with reduction in the levels of DA and DOPAC in the hippocampus, which is closely correlated with the cognitive development of the neonatal rats.

Abstract:Objective To investigate the pathogen infections of Mongolian gerbils raised in a conventional facility, and to provide a basis for the establishment of local standards for pathogen detection in Mongolian gerbils. Methods A total of 16 species of bacteria, 11 species of viruses and 8 species of parasites were detected in 30 gerbils raised in a conventional facility, according to the national standards of microorganism and parasite detection in mice and rats. Results Gerbils raised in this conventional facility were infected with lymphocytic choriomeningitis virus (a positive rate of 6.7%), sendai virus (3.3%), pneumonia virus of mice (100.0%), reovirus type Ⅲ (6.7%), mouse encephalomyelitis virus (10.0%), mycoplasma spp. (6.7%), Tyzzer's organism (6.7%) and Helicobacter spp. (56.7%), according to our antibody detection results. Meanwhile, the detected positive rate of Pasteurella pneumotropica was 3.3%, Staphylococcus aureus 10.0%, Escherichia coli O115 a, C, K (B) 6.7%, Tritrichomonas muris 100.0% and flagellates 100.0%. Conclusions The results of our study provide a reference for the establishment of classification standards for gerbils according to their pathogen and parasite infections.

Abstract:Objective To explore the acute toxicity effect of CKLF1-C19, a polypeptide of chemokine-like factor 1 (CKLF1), on the KM mice. Methods A total of 40 KM mice, half male and half female, were randomly divided into 2 groups. The mice in the experimental group were injected with CKLF1-C19 at a dose of 25 mL/kg (100 μg/mL, 1 mg/mL and 10 mg/mL) through the tail vein, and those in the control group received an equal volume of sterile saline solution. Changes in the body weight of the mice were recorded the day after treatment, and the general conditions of mice in the experimental group were observed closely and compared with the normal group. Then blood samples were taken from the abdominal aorta to measure liver and kidney function. Tissue samples of liver, kidney, spleen and lung were taken for histopathological examination by HE staining. Results In the maximum tolerance test, the mice of the two groups were in good condition, and their body weight was increased gradually, without significant difference between the experimental group and the control group (P > 0.05). There was no death within 14 days. The blood biochemical indexes of liver and kidney function showed no significant differences between the two groups (P > 0.05). The gross appearances of heart, liver, kidney, spleen and lung were normal in the two mouse groups, and the pathological examination with HE staining showed normal clear structure with no obvious changes in these organs of each group. Conclusions Our results demonstrate that CKLF1-C19 has no acute toxicity effect on mice.

Abstract:Objective To evaluate the sensitivity to 5 clinically commonly used anticancer drugs in vivo using the zebrafish xenotransplantation models of human lung cancer, stomach cancer, and liver cancer cells, respectively. Methods Zebrafish xenotransplantation models of A549 lung cancer cells, SGC-7901 stomach cancer cells and HepG2 liver cancer cells were established. The xenograft models of A549 cells were treated with three different doses of cis-platinum, paclitaxel, vinorelbine, endostar and bevacizumab, respectively. The SGC-7901 model was treated with three concentrations or doses of paclitaxel, irinotecan, hydroxyurea, cis-platinum and 5-fluorouracil, respectively. And the HepG2 model was treated with three concentrations or doses of adriamycin, gemcitabine, hydroxyurea, cis-platinum and 5-fluorouracil. The tumors were analyzed and quantified in vivo by fluorescence microscopy, and the inhibition rates of tumor growth with each drug were calculated and compared with the model control group for statistical significance. Results All of the tested anticancer drugs showed inhibitory effect on tumor cells in the zebrafish xenograft models with statistical significance in a dose-dependent manner. During the drug sensitivity test, the inhibition rate of bevacizumab on A549 lung cancer cells decreased in the order (65%) > cis-platinum (55%) > vinorelbine (40%) > endostar (39%) > paclitaxel (27%). As for the SGC-7901 stomach cancer cells, the tumor growth inhibition rate decreased in the order hydroxyurea (46%) > 5-FU (31%)=irinotecan (31%) > paclitaxel (26%) > cis-platinum (24%). And the therapeutic effect of cis-platinum on the HepG2 liver cancer cells decreased in the order (64%) > hydroxyurea (56%) > gemcitabine (46%) > adriamycin (45%) > 5-FU (38%). Conclusions Zebrafish xenotransplantation models of cancer cells are suitable for in vivo sensitivity test of anticancer drugs.

Abstract:Objective To screen the polymorphism microsatellite markers of guinea pigs, and provide basic information for identification of genetic structure and gene mapping in guinea pigs. Methods The genomic DNA of guinea pigs was found out on foreign websites, and microsatellite sequences characterized by AC/GT were selected. A total of 400 pairs of primers were designed using software according to their flanking sequences. After two rounds of PCR and electrophoresis, with the electrophoresis bands serving as genetic markers, the polymorphic primers were screened by the evaluation of microsatellite structure of guinea pigs. Results At the first step, 10 DNA samples from 5 strains of guinea pigs were taken for PCR, and 110 pairs of polymorphic microsatellite markers with 1-3 electrophoretic bands were screened from the designed 400 pairs of primers. At the second step, 60 DNA samples from 5 strains of guinea pigs were assayed by PCR and 51 pairs of polymorphic primers with high resolution electrophoresis bands were screened from the above 110 pairs of primers. Among these screened 51 primers, more than 10 pairs of primers showed accordant or mostly accordant differences among strains. Conclusions The 51 pairs of primers are polymorphic among individuals and strains, and have not been found in other reports so far.They can be used for conventional genetic detection and related studies, and some of them can be used for gene mapping of the traits in guinea pigs.

Abstract:Objective To explore the inhibitory effect and related mechanism of paeoniflorin on proliferation of hypertrophic scar (HS) fibroblasts. Methods HS fibroblasts were cultured with 0 (control), 200, 400, 800 μmol/L of paeoniflorin for 24, 48, and 72 h. Cell viability was detected by MTT assay. Cell apoptosis was detected using Hoechst staining. Cell cycle was measured by flow cytometry. The levels of type I collagen (COL I) and type Ⅲ collagen (COL Ⅲ) were detected by enzyme linked immunosorbent assay (ELISA). The expressions of transforming growth factor-β (TGF-β)/Smad signaling pathway related proteins, as well as matrix metalloproteinase 1 (MMP1) and MMP13 were detected by Western blot. Results 200, 400, 800 μmol/L of paeoniflorin reduced the cell viability of HS fibroblasts significantly (P< 0.01), with the nuclei turning pale and shrunken, and caused cell cycle arrest at G1 phase (P< 0.01). Moreover, the levels of COL I and COL Ⅲ in the cells were decreased significantly (P< 0.01), and the expressions of MMP1, MMP13, TGF-β1, p-Smad2 and p-Smad3 were down-regulated significantly (P< 0.01). Conclusions Paeoniflorin can obviously inhibit the proliferation and collagen synthesis of hypertrophic scar fibroblasts, probably through inhibition of the TGF-β1/Smad signaling pathway.

Abstract:Objective To express the recombinant IL-37b protein and to investigate its role in the regulation of immune responses. Methods The prokaryotic expression vector pET28/IL-37b was constructed. The recombinant IL-37b protein was induced to be expressed and was purified using Ni²⁺-NTA gel column. C57BL/6 J mice were treated with IL-37b and injected with lipopolysaccharide (LPS) to induce septic shock, and the expression levels of IL-1β, IL-6, IFN-γ in the serum of the mice were detected. Dendritic cells from bone marrow of the mice were isolated and cultured, and were treated with IL-37b. After LPS-induced activation, the expression levels of marker molecules such as CD40, CD80 and MHCⅡ on the cell surface, and cytokines such as IL-1β, IL-10, IL-12 and TNF-α in the culture supernatants were detected by flow cytometry. The CD4⁺ T cells from mice were isolated and the inhibitory effects of IL-37b on the expression of IFN-γ, TNF-α and IL-10 in the culture supernatants of T cells after induction by LPS were detected. Results IL-37b reduced the expression levels of proinflammatory cytokines in the serum of septic shock mice. IL-37b also inhibited the expression of co-stimulatory molecules and proinflammatory cytokines of the mouse dendritic cells, and suppress the activation of CD4⁺T cells in vitro. Conclusions Purified recombinant IL-37b protein has high bioactivity, and can alleviate septic shock in organisms through inhibiting the activation of dendritic cells and related T cell immune responses.

Abstract:Objective To study the therapeutic effect of sea buckthorn oil on allergic contact dermatitis (ACD) in mice. Methods A total of 60 ICR mice were randomly divided into 6 groups:blank control group, model control group, three groups of high-dose, medium-dose and low-dose sea buckthorn oil (100%, 50%, 25%, ad us. ext.), respectively, and positive control group (compound dexamethasone acetate cream), with 10 mice in each group. The mouse model of ACD was established by sensitization and stimulation with 2,4-dinitrochlorobenzene (DNCB), and injuries in the ear skin of the mice were scored and used as the indicator of successful establishment of the model. The degree of ear swelling and the spleen index of the mice in each group were measured at 48 h after stimulation. Hematoxylin and eosin staining was used to observe the pathological changes in the mouse ear skin. Results Measurement of the degrees of ear swelling showed that the high-dose sea buckthorn oil group (9 mL/kg, ad us. ext.) obviously inhibited the DNCB-induced ear swelling in the mice, with a significant difference compared with the model group (P< 0.01) and non-significant difference compared with the positive control group (P> 0.05). The result of the spleen index assessment showed that sea buckthorn oil at each dose may play an immune-regulatory role by promoting the development of immune organs. The pathological examination showed that epidermis thickening of the ear tissue, epidermal and dermal edema and infiltration of lymphocytes were reduced, dermal vasodilatation and congestion were alleviated, and inflammatory cell infiltration was inhibited in the three groups of different doses of sea buckthorn oil compared with the model control group. Conclusions Sea buckthorn oil has an obvious inhibitory effect on the DNCB-induced allergic contact dermatitis in mice. However, its related mechanisms remain to be further investigated.

Abstract:Objective To investigate the effect of bacillus Calmette-Guérin (BCG) on bladder cancer cells and their metabolites, and to preliminarily explore the possible mechanisms of BCG in the treatment of bladder cancer. Methods The rat model of bladder cancer was induced by intravesical instillation with N-methylnitrosourea (MNU). Bladder cancer cells and normal transitional epithelial cells were isolated and primarily cultured, and were divided into 5 groups according to the different components of the culture medium. The concentration of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in the supernatant of each group was detected by enzyme linked immunosorbent assay (ELISA). The concentration of BCG to inhibit the cancer cell growth was determined by MTT assay. Apoptosis of bladder cancer cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Results Among the 15 rats, 2 rats died after 2 times of instillation, and 3 rats died after 3 times of instillation, without obvious tumors found at autopsy. The other 10 rats were killed after completion of the intravesically instillation of MNU, and obvious tumors were found in 8 of them after dissection. The results of MTT assay showed that BCG had an inhibitory effect on the growth of bladder cancer cells, and the inhibitory rate was positively correlated with the concentration of BCG. The results of ELISA showed that the concentrations of TNF-α in the supernatant of groups B and D were (160.654±5.775) ng/L and (124.443±4.972) ng/L, respectively, with significant differences from those of the other three groups. The concentrations of IL-10 in the groups B and E were (16.973±3.428) ng/L and (20.327±2.721) ng/L, significantly higher than those of the other three groups. Apoptosis of cancer cells was not found in all groups. HE staining of the primary bladder cancer cells showed that the volume of cell nucleus was increased, and the nucleo-cytoplasmic ratio was increased. The number of nucleoli in some cells was increased and some nuclei appeared like ink drops with prominent nucleoli. Conclusions BCG has an inhibitory effect on the growth of rat bladder cancer cells. IL-10 and TNF-α secreted by the tumor cells might be involved in this regulatory process. However, apoptosis does not show an obvious effect on this inhibitory process.

Abstract:Objective To investigate the treatment and disposal of laboratory animal waste in Beijing area in 2016. Methods Questionnaire, telephone survey, on-the-spot investigation and WeChat were used to survey the basic situation and laboratory animal waste management, including bedding material, excreta, carcasses and experimental consumables, etc. in 164 laboratory animal facilities in Beijing area in 2016. Results The data we have collected were relatively comprehensive and universal, reflecting the currently existing problems. Conclusions This investigation provides a reference for the compilation of the management rules of laboratory animal waste in Beijing.

Abstract:Objective To evaluate the clinical effectiveness of venipuncture using the fluorescent intravenous indwelling catheter in dark environment in dog experiments. Methods Six dogs were randomly divided into three groups of two dogs each, and each dog was subjected to 40 times of venipuncture performed on a foreleg with normal intravenous indwelling catheter and fluorescent intravenous indwelling catheter, respectively, under high (101-105 lux), moderate (10.2-100 lux) or low (5-10 lux) brightness conditions. The success rates and time consumption of those two procedures were analyzed and compared statistically. Results The success rate and time consumption for venipuncture using fluorescent and normal intravenous indwelling catheter under low brightness were 82.5% and (204.36±13.13) s vs. 40.0% and (249.35±17.98) s, those performed under moderate (simulating morning and dawn) brightness were 90.0% and (194.86±8.60) s vs. 67.5% and (206.37±9.70) s, all showed a significantly higher efficiency of the venipuncture using fluorescent intravenous indwelling catheter (P < 0.05). Conclusions The use of fluorescent intravenous indwelling catheter has the advantages of higher success rate and shorter time consumption for venipuncture under low and moderate brightness conditions.

Abstract:Objective To establish a dual RT-PCR detection method for bovine viral diarrhea virus (BVDV) in bovine-derived samples. Methods The primers were designed and synthesized according to the published BVDV1 and BVDV2 genes containing highly conservative sequences in the 5' untranslated regions (5' UTR) to establish the dual RT-PCR method. The specificity, sensitivity, stability of this method were evaluated. Then 41 bovine-derived samples and 64 bovine plasma samples including bovine calf serum, deproteinized calf serum extract and one lienal polypeptide injection were detected with this method. Results There was no cross reaction with bovine parainfluenza virus type 3 (BPIV3), classical swine fever virus (CSFV) and Japanese encephalitis virus (JEV) when samples were detected with the established dual RT-PCR method. The lowest concentration of template DNA for detection of BVDV1 and BVDV2 was 8.87×10² copies and 6.31×10² copies per microliter, respectively. Electrophoresis bands of about 151 bp and 303 bp were still amplified and detected after the BVDV1 and BVDV2 cDNA was stored at -30℃ for 12 months. The BVDV positive rate of 41 bovine-derived samples and 64 bovine plasma samples detected with this dual RT-PCR method was 14.6% and 29.7%, respectively. Conclusions The established dual RT-PCR method has the advantages of high efficiency, specificity, sensitivity and stability, and can be used for the detection of BVDV in bovine-derived samples.

Abstract:Objective To simplify and optimize the method for isolation and culture of primary mouse hepatocytes on the basis of conventional extraction method, and to provide a reference for related research. Methods Mouse liver was reversely perfused with the isolation solution (i.e., through the vena cava inferior in, and portal vein out), cut into small pieces and digested with enzymes. Then the hepatocytes were isolated by density gradient centrifugation and transferred into culture medium. The cell viability was detected by trypan blue staining. The purity of the hepatocytes was analyzed by flow cytometry and the cell morphology was observed with an inverted microscope. Results The hepatocytes obtained by this improved method showed high viability and purity, with typical characteristics of cell morphology. Conclusions The liver perfusion is facilitated by reversed perfusion, and the isolated hepatocytes are with high viability and purity confirmed by many times of experiments. This optimized procedure is an easy and efficient method for isolation of primary mouse hepatocytes.

Abstract:Objective To improve the preparation of bronchoalveolar lavage fluid (BALF) in mice. Methods BALB/c mice were divided into 3 groups. In the first and second groups, the whole lung lavage was performed with the traditional method, using a vein detained needle and lavaged with sterile saline. The mice in the third group got whole lung lavage by the improved method, namely, using a self-made plastic rigid pipe connected with a syringe. Each mouse was lavaged for 3 times, with 0.5 mL of sterile saline for each time, and the time consumption was recorded. The collected BALF was centrifuged, the supernatant was separated and its volume was measured accurately. Results The time spent for BALF collection in each mouse in the third group was (4±0.62) min, significantly shorter than that of (10±0.75) and (12±0.88) min, respectively in the first and second groups (P< 0.05). The volume of BALF collected in each mouse of the third group was (1.34±0.16) mL, significantly higher than that of (1.03±0.25) and (1.13±0.22) mL, respectively in the first and second groups (P< 0.05). Conclusions The improved method of BALF collection described in our study is simple, economical and efficient, and is useful for beginners especially.

Abstract:Objective To explore the practical value of a modified method for blood collection from the inner canthus of mice using a pipettor. Methods A total of 20 male C56BL/6J mice were divided into two groups, the pipettor group and the capillary group (10 mice in each group). Blood samples were taken 3 times from the inner canthus of the mice with a pipettor or glass capillary, respectively, and the time-consumption and success rate of the two groups were recorded and compared. Results The success rates of both the blood collection methods were 100%. However, in the pipettor group, the blood collection was completed faster than the capillary group with a significant difference (P < 0.05). Conclusions It is a relatively simple and safe method for blood collection from the inner canthus of mice using a pipettor.

Abstract:Laboratory animals are commonly used as experimental objects in medical research, and laboratory animal welfare is closely related with good scientific outcomes. It is important for researchers in hospitals to establish a concept of protecting the welfare of laboratory animals. In this paper, combined with our experience concerning with the ethics and animal welfare in recent years in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, we try to discuss the importance of animal experiments in the hospital, the significance of maintenance of laboratory animal welfare and the ethical review of the welfare of laboratory animals, etc., in order to provide a reference to the protection of laboratory animal welfare for researchers in hospitals.

Abstract:Objective To investigate the current status of mouse euthanasia methods in China, and to provide the reference and basis for the administrative authorities of laboratory animal management to master the implementation of "euthanasia" and formulate related policies. Methods Research papers containing the terms of "mouse" and "execution" in Chinese characters during the period from 2015 to 2016 were searched in Wanfang database, and statistical analysis was performed with the articles meeting the searching criteria. Results A total of 890 research articles met the searching criteria, of which 351 articles clearly described the killing method, accounting for only 39.44%. The mouse-killing methods included cervical dislocation, decapitation, exsanguination and sampling after anesthesia, excessive anesthesia, abdominal aorta bleeding and carbon dioxide asphyxiation, among them cervical dislocation accounted for the highest rate, 75.78%. Conclusions The current implementation of mouse euthanasia methods in our country has been far from optimistic. The mouse euthanasis methods have often been ignored in scientific articles and the description of the methods is not standardized. In order to promote the effective implementation of the regulations related to mouse euthanasia, it is needed to promote the study of related techniques and to strengthen personnel training.

Abstract:The precision medical research in China is moving towards a new vigorous development stage. As an important contributor to clinical research, laboratory animals are becoming the key support and important guarantee to promote the development of precision medical diagnosis and treatment. At present, the evaluation system for animal experiments in China is not perfect enough, especially in the field of precision medicine. Under the background of domestic research and policy drive, we should learn from foreign experience and grasp the opportunities to promote and improve the evaluation system suitable for animal experiments in China.

Abstract:Over the past few decades, the classification of oncogenes or tumor suppressor genes has been an important topic in cancer biology. However, it is difficult to classify some genes. Heterogeneous nuclear ribonucleoprotein K (HNRNPK) is a nucleic acid-binding protein, which is involved in the regulation of gene expression, signal transduction and many other cellular processes. In recent years, it has been found that HNRNPK is overexpressed in many types of tumors, and its overexpression is negatively correlated with the prognosis of patients, suggesting that HNRNPK may play a role as an oncogene in tumorigenesis. In contrast, however, HNRNPK has also been considered as a tumor suppressor gene in acute myeloid leukemia (AML). Therefore, in this article we summarize and discuss the recent progress in the molecular functions and regulatory mechanisms of HNRNPK in tumorigenesis and progression.

Abstract:Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis (MTB), is the outcome of the interaction between polygenes and environmental factors, which has been shown in lots of genetic studies. In recent years, the research of TB susceptibility genes and their single nucleotide polymorphism (SNP) loci has become a hot topic, but genes and SNPs exactly associated with TB susceptibility are rarely reported. What's more, some susceptibility genes are different among races, populations and geographical distributions, resulting in inconsistency, or even contrary conclusions drawn from local studies of different populations or areas. In order to obtain susceptibility genes that are widely applicable and exactly associated with TB, it is necessary to screen the genes preliminarily in the laboratory animals with gene diversity, and thereafter, verify those genes in animals or humans. The Collabrative Cross (CC) mice have the advantages of diverse and clear genetic background, which can provide a new tool for the research of TB susceptibility. This review summarizes the advances in the studies of TB susceptibility genes and their SNPs, and looking forward to the application of CC mice in these studies and its significance.