Carboxylesterase 1 family knockout alters drug disposition and lipid metabolism

The mammalian carboxylesterase 1 (Ces1/CES1) family comprises several enzymes that hydrolyze many xenobiotic chemicals and endogenous lipids. To investigate the pharmacological and physiological roles of Ces1/CES1, we generated Ces1 cluster knockout (Ces1 -/- ) mice, and a hepatic human CES1 transgenic model in the Ces1 -/- background (TgCES1). Ces1 -/- mice displayed profoundly decreased conversion of the anticancer prodrug irinotecan to SN-38 in plasma and tissues. TgCES1 mice exhibited enhanced metabolism of irinotecan to SN-38 in liver and kidney. Ces1 and hCES1 activity increased irinotecan toxicity, likely by enhancing the formation of pharmacodynamically active SN-38. Ces1 -/- mice also showed markedly increased capecitabine plasma exposure, which was moderately decreased in TgCES1 mice. Ces1 -/- mice were overweight with increased adipose tissue, white adipose tissue inflammation (in males), a higher lipid load in brown adipose tissue, and impaired blood glucose tolerance (in males). These phenotypes were mostly reversed in TgCES1 mice. TgCES1 mice displayed increased triglyceride secretion from liver to plasma, together with higher triglyceride levels in the male liver. These results indicate that the carboxylesterase 1 family plays essential roles in drug and lipid metabolism and detoxification. Ces1 -/- and TgCES1 mice will provide excellent tools for further study of the in vivo functions of Ces1/CES1 enzymes.

Transformation Models for Characterization of Cancer Driver Genes / 中国生物化学与分子生物学报

The development of cancer is a complex process. Although many genetic and epigenetic alterations are detected in cancer cells, only small proportion of these alterations may function as cancer drivers. Because it is difficult to directly characterize driver factors in human body, alternative research models have continuously been developed. In the early stage from 1915 to 1980s, genetic activation of proto-oncogenes and inactivation of tumor suppressor genes were often characterized using various carcinogenicity tests, including animal tumor induction models, malignant transformation of normal human cells/tissues/organs cultured in vitro or transplanted into immuno-defected mice. Since 1990 to now, gene transfection and knockout technologies were frequently used to characterize cancer driver genes. Currently, 2-dimensional (2D) or 3-dimensional (3D) cell culture and organoid are also employed to test carcinogenicity of environmental factors and driver genes. In this review, we summarized the main models of malignant transformation and their advantages and disadvantages.

Establishment of a gp120 transgenic mouse model with 7 nAChR knockout / 南方医科大学学报

OBJECTIVE@#To construct a HIV-1 gp120 transgenic mouse model (gp120) with 7 nicotinic acetylcholine receptor (7nAChR) gene knockout.@*METHODS@#The 7nAChR gene knockout mice (7R) were crossed with HIV-1gp120 transgenic mice (gp120) to generate F1 generation mice. We selected the F1 mice with the genotype of 7R/gp120 to mate to obtain the F2 mice. The genotypes of the F3 mice were identified by PCR, and the protein expressions in the double transgenic animal model was analyzed by immunohistochemistry. BV2 cells were treated with gp120 protein and 7nAChR inhibitor, and the expressions of IL-1β and TNF- were detected using ELISA.@*RESULTS@#The results of PCR showed the bands of the expected size in F3 mice. Two F3 mice with successful double gene editing (7R/gp120) were obtained, and immunohistochemistry showed that the brain tissue of the mice did not express 7 nAChR but with high gp120 protein expression. In the cell experiment, treatment with gp120 promoted the secretion of IL-1β and TNF- in BV2 cells, while inhibition of 7nAChR significantly decreased the expression of IL-1β and TNF- ( < 0.001).@*CONCLUSIONS@#By mating gp120 Tg mice with 7R mice, we obtained gp120 transgenic mice with 7nAChR gene deletion, which serve as a new animal model for exploring the role of 7nAChR in gp120-induced neurotoxicity.

Impact of autologous whole blood administration upon experimental mouse models of acute Trypanosoma cruzi infection

Background: Autologous whole blood (AWB) administration is described as alternative/complementary medical practice widely employed in medical and veterinary therapy against infections, chronic pathologies and neoplasias. Our aim is to investigate in vivo biological effect of AWB using healthy murine models under the course of Trypanosoma cruzi acute infection. Methods: The first set of studies consisted of injecting different volumes of AWB and saline (SAL) into the posterior region of quadriceps muscle of healthy male Swiss mice under distinct therapeutic schemes evaluating: animal behavior, body and organ weight, hemogram, plasmatic biochemical markers for tissue damage and inflammatory cytokine levels and profile. To assess the impact on the experimental T. cruzi infection, different schemes (prior and post infection) and periods of AWB administration (from one up to 10 days) were conducted, also employing heterologous whole blood (HWB) and evaluating plasma cytokine profile. Results: No major adverse events were observed in healthy AWB-treated mice, except gait impairment in animals that received three doses of 20 L AWB in the same hind limb. AWB and SAL triggered an immediate polymorphonuclear response followed by mononuclear infiltrate. Although SAL triggered an inflammatory response, the kinetics and intensity of the histological profile and humoral mediator levels were different from AWB, the latter occurring earlier and more intensely with concomitant elevation of plasma IL-6. Inflammatory peak response of SAL, mainly composed of mononuclear cells with IL-10, was increased at 24 h. According to the mouse model of acute T. cruzi infection, only minor decreases ( 30%) in the parasitemia levels were produced by AWB and HWB given before and after infection, without protecting against mortality. Rises in IFN-gamma, TNF-alpha and...

Mouse models of breast cancer in preclinical research / 한국실험동물학회지

Breast cancer remains the second leading cause of cancer death among woman, worldwide, despite advances in identifying novel targeted therapies and the development of treating strategies. Classification of clinical subtypes (ER+, PR+, HER2+, and TNBC (Triple-negative)) increases the complexity of breast cancers, which thus necessitates further investigation. Mouse models used in breast cancer research provide an essential approach to examine the mechanisms and genetic pathway in cancer progression and metastasis and to develop and evaluate clinical therapeutics. In this review, we summarize tumor transplantation models and genetically engineered mouse models (GEMMs) of breast cancer and their applications in the field of human breast cancer research and anti-cancer drug development. These models may help to improve the knowledge of underlying mechanisms and genetic pathways, as well as creating approaches for modeling clinical tumor subtypes, and developing innovative cancer therapy.

Combining Human and Rodent Genetics to Identify New Analgesics / 神经科学通报·英文版

Most attempts at rational development of new analgesics have failed, in part because chronic pain involves multiple processes that remain poorly understood. To improve translational success, one strategy is to select novel targets for which there is proof of clinical relevance, either genetically through heritable traits, or pharmacologically. Such an approach by definition yields targets with high clinical validity. The biology of these targets can be elucidated in animal models before returning to the patients with a refined therapeutic. For optimal treatment, having biomarkers of drug action available is also a plus. Here we describe a case study in rational drug design: the use of controlled inhibition of peripheral tetrahydrobiopterin (BH4) synthesis to reduce abnormal chronic pain states without altering nociceptive-protective pain. Initially identified in a population of patients with low back pain, the association between BH4 production and chronic pain has been confirmed in more than 12 independent cohorts, through a common haplotype (present in 25% of Caucasians) of the rate-limiting enzyme for BH4 synthesis, GTP cyclohydrolase 1 (GCH1). Genetic tools in mice have demonstrated that both injured sensory neurons and activated macrophages engage increased BH4 synthesis to cause chronic pain. GCH1 is an obligate enzyme for de novo BH4 production. Therefore, inhibiting GCH1 activity eliminates all BH4 production, affecting the synthesis of multiple neurotransmitters and signaling molecules and interfering with physiological function. In contrast, targeting the last enzyme of the BH4 synthesis pathway, sepiapterin reductase (SPR), allows reduction of pathological BH4 production without completely blocking physiological BH4 synthesis. Systemic SPR inhibition in mice has not revealed any safety concerns to date, and available genetic and pharmacologic data suggest similar responses in humans. Finally, because it is present in vivo only when SPR is inhibited, sepiapterin serves as a reliable biomarker of target engagement, allowing potential quantification of drug efficacy. The emerging development of therapeutics that target BH4 synthesis to treat chronic pain illustrates the power of combining human and mouse genetics: human genetic studies for clinical selection of relevant targets, coupled with causality studies in mice, allowing the rational engineering of new analgesics.

Research progress of muscle atrophy animal models / 中国药理学通报

An effective therapeutic method for muscular dystro-phy is unavailable now;however,the research and development of anti-muscular dystrophy drugs need appropriate animal mod-els. Researchers focus on Caenorhabditis elegans because of the andvantages such as the transparent body, short life cycle, and high homology with human genes. The Caenorhabditis elegans mutant strains show musucular dystrophy phenotype similar to human diseases. In this paper,the application of Caenorhabditis elegans models in muscular dystrophy research has been re-viewed.

Impact of autologous whole blood administration upon experimental mouse models of acute Trypanosoma cruzi infection

Autologous whole blood (AWB) administration is described as alternative/complementary medical practice widely employed in medical and veterinary therapy against infections, chronic pathologies and neoplasias. Our aim is to investigate in vivo biological effect of AWB using healthy murine models under the course of Trypanosoma cruzi acute infection. Methods: The first set of studies consisted of injecting different volumes of AWB and saline (SAL) into the posterior region of quadriceps muscle of healthy male Swiss mice under distinct therapeutic schemes evaluating: animal behavior, body and organ weight, hemogram, plasmatic biochemical markers for tissue damage and inflammatory cytokine levels and profile. To assess the impact on the experimental T. cruzi infection, different schemes (prior and post infection) and periods of AWB administration (from one up to 10 days) were conducted, also employing heterologous whole blood (HWB) and evaluating plasma cytokine profile. Results: No major adverse events were observed in healthy AWB-treated mice, except gait impairment in animals that received three doses of 20 µL AWB in the same hind limb. AWB and SAL triggered an immediate polymorphonuclear response followed by mononuclear infiltrate. Although SAL triggered an inflammatory response, the kinetics and intensity of the histological profile and humoral mediator levels were different from AWB, the latter occurring earlier and more intensely with concomitant elevation of plasma IL-6. Inflammatory peak response of SAL, mainly composed of mononuclear cells with IL-10, was increased at 24 h. According to the mouse model of acute T. cruzi infection, only minor decreases (< 30%) in the parasitemia levels were produced by AWB and HWB given before and after infection, without protecting against mortality. Rises in IFN-gamma, TNF-alpha and IL-6 were detected at 9 dpi in all infected animals as compared to uninfected mice but only Bz displayed a statistically significant diminution (p= 0.02) in TNF-alpha levels than infected and untreated mice. Conclusions: This study revealed that the use of autologous whole blood (AWB) in the acute model employed was unable to reduce the parasitic load of infected mice, providing only a minor decrease in parasitemia levels (up to 30%) but without protecting against animal mortality. Further in vivo studies will be necessary to elucidate the effective impact of this procedure.(AU)

Establishment of a nude mouse model of glioma orthotopic xenograft with double-fluorescent labeling / 中国比较医学杂志

Objective To establish a stable and real-time monitorable nude mouse model of orthotopic glioma xenograft.Methods U251 glioma cell line was infected by a lentiviral vector containing green fluorescent protein (GFP) and luciferase (Luc) gene.Cells stably expressing fluorescence of GFP and Luc were sorted by flow cytometry.CCK-8 test and Transwell tumor invasion and migration assay were used to compare the biological features between the cells stably expressing GFP-Luc fluorescence and cells without fluorescence.Then the cells were implanted intracranially in the right caudate nucleus of athymic Balb/c nude mice to establish the tumor model.The growth of intracerebral tumor was monitored over time by a bioluminescence imaging (BLI) system.Hematoxylin-eosin (HE) staining was used to evaluate the histopathological features and tumorigenicity of the transplanted glioma cells in the brain of nude mice.Results U251 glioma cell line with stably expressing GFP-Luc fluorescence and the corresponding orthotopic xenograft model were successfully established.There was no statistically significant difference in the proliferation,invasion and migration abilities between the cells with stably expressing GFP-Luc fluorescence and the control cells.This model showed a high tumor formation rate and stable tumor growth,and takes a moderate time to establish this model.Conclusions Compared with the traditional glioma cells,GFP-Luc-transfected human glioma cells are more feasible for the studies of glioma in vivo.The tumor growth and pathological characteristics in this U251-GFP-Luc glioma model are similar to human glioma,and the growth of this tumor can be real-time monitored.It can be used as an ideal animal model for experimental studies of glioma.

Establishment of a mouse model of kidney deficiency induced by oral administration of hydrocortisone and evaluation of related factors / 中国实验动物学报

Objective To establish a mouse model of kidney-yin and kidney?yang deficiency after oral administra?tion of hydrocortisone, and to explore the related evaluation factors. Methods The model was established by oral adminis?tration of hydrocortisone to induce kidney?yin and kidney?yang deficiency in mice. The survival and body weight of the mice were observed. The serum content of adrenal cortical hormone ( ACTH) , cortisol ( Cor. ) in the hypothalamic?pituitary?ad?renal (HPA) axis, and thyroid stimulating hormone (TSH), triiodothyronine (T3), thyrox (T4) in the hypothalamic?pi?tuitary?thyroid (HPT) axis, follicle?stimulating hormone (FSH), estradiol (E2), testosterone (T) in the hypothalamic?pituitary?gonadal ( HPG) axis were determined by radioimmunoassay. Results The body weight of kidney?yin and kidney?yang mice were decreased, the serum ACTH, Cor, TSH, T3, T4 contents were decreased, the serum FSH, E2, T contents were increased in the kidney?yang deficiency model mce ( P<0. 01 ) , and those parameters in the kidney?yin deficiency model mice were changed in opposite direction. Conclusions It is found that the hormone levels of ACTH, Cor, TSH, T3, T4, FSH, E2 and T in kidney deficiency mice are changed, and cortisol can be used as an important index to evaluate the model of kidney deficiency induced by glucocorticoid.

Research progress of humanized mouse models in immune system / 中国比较医学杂志

Animal model is an animal material with human mimic performance established in biomedical scientific research. It can be used as experimental basis for studies of experimental hypothesis and clinical hypothesis. It can shorten the research time and observe the whole process of disease occurrence, development or prevention and treatment. Human biomedical research is largely limited by the biological complexity. In order to overcome this limitation, based on the immunosuppressive characteristics of a severely immunodeficient ( SCID) or recombinant activated gene ( Ragnul ) in mice, humanized mouse models of human diseases can be established and have been widely used to study the underlying principles of human immunobiology and complex pathological mechanisms of human diseases. This approach has become one of the important ways to promote the development of medical sciences, with practicality and foresight. In this paper, the application and research progress of humanized mouse models are reviewed.

Research progress of humanized mouse models in immune system / 中国比较医学杂志

Animal model is an animal material with human mimic performance established in biomedical scientific research. It can be used as experimental basis for studies of experimental hypothesis and clinical hypothesis. It can shorten the research time and observe the whole process of disease occurrence, development or prevention and treatment. Human biomedical research is largely limited by the biological complexity. In order to overcome this limitation, based on the immunosuppressive characteristics of a severely immunodeficient ( SCID) or recombinant activated gene ( Ragnul ) in mice, humanized mouse models of human diseases can be established and have been widely used to study the underlying principles of human immunobiology and complex pathological mechanisms of human diseases. This approach has become one of the important ways to promote the development of medical sciences, with practicality and foresight. In this paper, the application and research progress of humanized mouse models are reviewed.

Establishment of patient-derived tumor xenograft (PDTX) models using samples from CT-guided percutaneous biopsy

This study aimed to investigate the feasibility of the establishment of a human cancer xenograft model using samples from computed tomography (CT)-guided percutaneous biopsy. Fresh tumor tissues obtained from 10 cancer patients by CT-guided percutaneous biopsy were subcutaneously inoculated into NOD-Prkdcem26Il2rgem26Nju (NCG) mice to establish human patient-derived tumor xenograft (PDTX) models. The formation of first and second generation xenografts was observed, and tumor volume was recorded over time. Tumor tissue consistency between the PDTX model and primary tumors in patients was compared using H&E staining and immunohistochemistry. Pharmacodynamic tests of clinically used chemotherapeutic drugs were conducted on second generation xenografts, and their effects on tumor growth and body weight were observed. CT-guided percutaneous biopsy samples were successfully collected from 10 patients with advanced cancers. The PDTX model was established in mice using tumor samples obtained from 4 cancer patients, including one small cell carcinoma sample, two adenocarcinoma samples, and one squamous cell carcinoma sample. The success rate was 40%. The obtained PDTX model maintained a degree of differentiation, and morphological and structural characteristics were similar to primary tumors. The pharmacodynamic test of chemotherapeutic drugs in the PDTX model revealed a therapeutic effect on tumor growth, as expected. CT-guided percutaneous biopsy samples can be effectively used to establish a PDTX model, and test these chemotherapy regimens.

Establishment of a mouse model of cutaneous squamous cell carcinoma induced by 7,12-DMBA, croton oil and narrow-band ultraviolet B irradiation / 中国比较医学杂志

Objective To establish a mouse model of cutaneous squamous cell carcinoma induced by 7,12-dimethylbenz(a)anthracene (7,12-DMBA)/croton oil and narrow-band ultraviolet B (NB-UVB) irradiation.Methods A total of fifty 6-8-week old BALB/c mice (male:female 1:1) were randomly divided into three experimental groups.The group A was treated with chemical carcinogens alone, group B was treated with NB-UVB alone, and group C was treated with chemical carcinogens plus NB-UVB.The general status and skin appearance of mice were observed during the experiment.The survival rate and tumor formation rate of each group was calculated at weeks 5, 10, 15, and 20. Pathological examination was carried out to observe the histological changes of skin lesions.Results Papules measuring≥l mm in diameter began to develop in some mice of the group C at 5 weeks after the first treatment with chemical carcinogens.The tumor formation rates at 20 weeks after treatment were 86.67%, 7.14%, 94.12%in the groups A, B, C, respectively.Pathological examination revealed characteristic changes of squamous cell carcinoma in 13.34%, 0%, 70.59%of the mice in the group A, B, C, respectively.Conclusions Establishment of a mouse model of cutaneous squamous cell carcinoma induced by 7,12-DMBA/croton oil and NB-UVB is a better method than treated with chemical carcinogens alone or NB-UVB alone.This method can increase the tumor formation rate and incidence rate of SCC, and within a shorter period.

Characterization of a Trpc6 Transgenic Mouse Associated with Early Onset FSGS.

Rationale: Mutations in Transient Receptor Potential Channel 6 (TRPC6) gene are associated with autosomal dominant focal and segmental glomerulosclerosis (FSGS). The majority of the identified mutations affect the ion channel function. Since calcium channels are promising candidate drug targets, there is an an urgent need for a mouse model to assess new therapeutic drugs and to help delineate the pathogenic process leading to FSGS. We have previously reported the generation of three independent transgenic mouse lines carrying different Trpc6 mutations that display a glomerular disease comparable to the phenotype presented by individuals with FSGS. However, the utility of these models for drug testing is dampened by the late-onset of the presentation and the mild phenotypic manifestations. Methodology: In order to obtain a time-effective mouse model for Trpc6-associated FSGS we generated a new transgenic mutant Trpc6 mouse model emulating the amino acid change carried by the first pediatric patient of FSGS associated with a TRPC6 mutation: M132T. Results: Mice carrying the orthologous Trpc6 M131T transgene showed early onset proteinuria and early signs of FSGS. When exploring molecular consequences of the overexpression of this mutated form of Trpc6 in podocytes, differences in expression levels of Axin2 and β-catenin were found in glomeruli from transgenic Trpc6 M131T mice. These data supports the proposed molecular mechanisms related to the activation of calcineurin-NFAT/Wnt signaling, as outcome of the increased calcium influx caused by the mutated form of Trpc6. Conclusion: Given that the Trpc6 M131T mouse develops an early onset of FSGS-like phenotypes it represents a promising model for studying the pathogenesis of FSGS caused by TRPC6, facilitating the assessment of new drugs as treatments and allowing further studies to understand underlying molecular pathways involved in the development of the TRPC6 mediated disease.

Cyclophosphamide-induced immunosuppressive mouse models established under different conditions and mathematical modeling analysis with partial least squares / 中国比较医学杂志

ObjectiveComparingfourgroupsofimmunosuppressivemousemodelsestablishedby cyclophosphamide administration in different doses and periods , we used partial least squares ( PLS) analysis to evaluate the immunosuppressive mouse models comprehensively and select the appropriate way to establish this model .Methods In this experimental study, 58 male KM mice were randomly divided into five groups: normal group (10 mice) were given normal saline daily by i.p.injection, model group 1 (12 mice) was given 40 mg/kg CTX daily by i.p.injection for 10 days, model group 2 (12 mice) was given 80 mg/kg CTX daily by i.p.injection for 3 days, model group 3 (12 mice) was given 40 mg/kg CTX daily by i.p.injection twice for a week, model group 4 (12 mice) was given 50 mg/kg CTX daily by i.p.injection for 7 days.After the injection of cyclophosphamide , the daily metabolic activities were detected everyday such as body weight , water intake , and food intake , organ index and immunological indexes such as blood RT of the model mice were measured as well .Using partial least squares ( PLS) analysis to the models and analyzing the final weight , final anal temperature , organ index , and blood routine examination in order to evaluate the immunosuppressive mouse models comprehensively .Results Compared with the normal group , different dosages of CTX reduced the weight and anal temperature of model mice (P<0.05), the food intake and water intake (P<0.01), and the spleen index and thymus index ( P<0.01 ) .Besides , the amount and percentage of basophilic granulocytes decreased ( P <0.05 ) , and the percentage of MCHC , macrophage went up , as well as the absolute value of WBC and lymphocytes were decreased in the model groups 1, 2, and 4 (P<0.05).According to the PLS analysis, there were significant differences among models 1, 2, and 4 when compared with the normal group , especially the most different in the model group 1.Conclusions After the PLS analysis of different indexes , the optimal way to establish immunosuppressive mouse models is the procedure with 40 mg/kg CTX daily injected i .p.for ten days .Our findings provide experimental evidence for the establishment of immunosuppressive mouse models .

Genetically Engineered Mouse Models for Drug Development and Preclinical Trials

Drug development and preclinical trials are challenging processes and more than 80% to 90% of drug candidates fail to gain approval from the United States Food and Drug Administration. Predictive and efficient tools are required to discover high quality targets and increase the probability of success in the process of new drug development. One such solution to the challenges faced in the development of new drugs and combination therapies is the use of low-cost and experimentally manageable in vivo animal models. Since the 1980's, scientists have been able to genetically modify the mouse genome by removing or replacing a specific gene, which has improved the identification and validation of target genes of interest. Now genetically engineered mouse models (GEMMs) are widely used and have proved to be a powerful tool in drug discovery processes. This review particularly covers recent fascinating technologies for drug discovery and preclinical trials, targeted transgenesis and RNAi mouse, including application and combination of inducible system. Improvements in technologies and the development of new GEMMs are expected to guide future applications of these models to drug discovery and preclinical trials.

La trisomía 21: 50 años después de lejeune / the 21-trisomy: 50 years after lejeune

El síndrome de Down, es la causa más frecuente de discapacidad intelectual, fue descrito por primera vez en el año 1886, durante una era de grandes cambios en el conocimiento de la genética y la evolución. Ocurre con una frecuencia de 1 por cada 700 nacidos vivos. En muchos casos la historia de la investigación en el síndrome de Down cursa paralela a la historia de la genética humana y ha sido fuente de grandes progresos en esta ciencia. En esta revisión se describe la interrelación entre los avances del conocimiento de la genética y el conocimiento del síndrome de Down tomando en consideración el impacto del descubrimiento de su etiología realizado en 1959 por Jerone Lejeune. Con motivo de la celebración de los 50 años de este acontecimiento, se escogió este descubrimiento como marcador de división cronológica de las etapas de producción del conocimiento sobre el síndrome, obteniéndose la era pre y pos-Lejeune, desde su descripción inicial al presente y sobre la base de esta perspectiva histórica se especula brevemente acerca del futuro de la investigación en el síndrome de Down

Down syndrome, is the most common cause of intellectual disabilities, it was first described in 1866, during an era of great change in understanding of genetics and evolution. It occurs in about I of every 700 newborns. In many instances, The history of research on Down syndrome courses parallels with the history of human genetics and it has inspired progress in human genetics. In this revision, it is described the interplay between advances in the understandins of genetics and the understanding of the Down syndrome and it was considered the finding of its etiology by Jerone Lejeune in 1959, as the index, Fifty years the discovery of the origin of the Down syndrome, it has been utilized for the division of two eras in the generation of knowledge in Down syndrome, the pre and the post-Lejeune era, from its initial description to the present, and on the basis of this historical perspective, speculate briefly about the future of research on Down syndrome

Animal models of colorectal cancer and liver metastases / 国际外科学杂志

The liver is the most common site of distant metastasis of colorectal cancer. In order to study colorectal cancer metastasis to the liver, establishing and choosing appropriate mouse model is crucially im-portant. In this review, we mainly discuss the mouse models of colorectal cancer and liver metastases: Tumor fragments or cancer cells orthotopic transplant to eoloncecal part, injecting cancer cells into the spleen, portal injection of cancer cells, colorectal cancer implantation to the subcapsular of the liver.