摘要: 目的　建立一个部分模拟临床病理的简便易得、经济有效的用于筛选和研制抗焦虑药的模型。方法　用间氯苯哌嗪 (mCPP)诱导产生焦虑 ,观察ddy小鼠和ICR小鼠在明暗箱的行为表现。结果　mCPP在SC 1- 4mg kg的剂量下即可显著降低ddy小鼠在明箱的活动次数 ,而对暗箱的活动次数影响不显著 ;1mg kg与 4mg kg组比较 ,在明箱的活动次数无显著差异 ;mCPP在SC 2 - 10mg kg的剂量下对ICR小鼠在明箱的的活动次数影响不太显著 ,只在10mg kg剂量下才显著 ;而对暗箱的活动次数却影响较大 ,在 2mg kg的剂量下即可显著降低活动次数。用安定对该模型进行验证 ,发现只用较小的样本量即可得出显著结果。结论　用ddy小鼠可以取代Wistar大鼠建立mCPP诱导焦虑的明暗箱模型 ,在样本量较小的情况下即可得到有效结果。所以是一个能够克服大鼠实验缺点的、简便易得且经济有效的用于筛选和研制抗焦虑药的良好模型。但用mCPP诱导的焦虑模型对小鼠的种属有选择性 ,ICR小鼠不适于上述模型。

摘要: Transgenic animal model for diseases established to show diversified disease through the expression or excessive expression of gene. The lipid metabolizing is very a complex physiological process in human. During the gene relating lipid metabolizing, it includes the factors of causing arteriosclerosis formed and the factors of reducing arteriosclerosis attack. This paper described the transgenic animal model and its characters of gene of aplipoprotein (Apo) such as ApoE, ApoA, ApoB, ApoC, receptor gene sweeping receptor SR A, SR B and SR CD, gene of lipid metabolizing enzyme, gene of transprotein such as CETP, LPL etc. Those transgenic animal models play an important role in studying disease mechanism, drug screening, gene treatment and in producing the protein as drug using.

摘要: The previous study of Smad3 gene knockout mice ( Smad3 ex8/ex8 )shows that the Smad3 ex8/ex8 mice develop progressive leukocytosis, periodontitis, gastritis, colitis and chronic infection with abscess formation adjacent to mucosal surfaces .symptomatic mutant mice exhibit thymic involution, enlarged lymph nodes and T cells with activated phenotype. Further study suggests that the thymic cells and peripheral T ceels of Smad3 ex8/ex8 mice have lost the response to TGF β.Furthermore, nwe found that the homologous Smad3 ex8/ex mice developed degenerative joint disease resembling human osteoarthritis, osteoporosis and wound healing up quicker. So the mice can serve as an ideal animal model for immune dysregulation, osteoarthritis and so on. To futher study the important role of Smad3 during the vertebrate development ,we charactered the genotype and reproduce the Smad3 knockout mice .Compare to the general experimental mice, the mice of genetic modifications is different in the breeding and reproduction. Besider the reproduction of inbred lines, we also must keep the mice inherit the mutant gene and consider the influence of mutant gene to the mouse's reproduction. Using PCR and Southern blot to characterize the genotype of the offspring can solve the question .Just like the homozygote of Smad3 ex8/ex8 mice lacking fertility, the homozygous mice cann't be used for propagating. We use the heterozygous mice for propagating, while the homozygous and wild type mice were used for phenotype analysis. The Smad3 ex8/ex8 heterzyous mice were used for breeding. With genotype being characterized, we found that the ratio of 3 genotype of the Smad3 ex8/ex8 heterzyous mice' offsprings fits the Mendel's laws. Their gestation is the sames as others mice,and embryo interval and litter are not different from others, We kept means of cryopreservation by vitrification of embryos and got normal conditions .Using the Smad3 ex8/ex8 heterzyous mice for propagating, we can be used for keeping breed and propagating.

摘要: the experimental animals is important materials and methods in life science research.. Almost all of drugs used in humanbeing are produced based on test in experimental animals. Various kinds of animal models are needed in the research fields of radiobiology, oncology and immunology, etc. Through hybridization between compatriot brother and sister for 20 generations continuously, we breed successfully IRM 2 inbred mouse whose paternal strain is 615 inbred mouse and maternal strain is ICR/JCL mouse. IRM 2 mouse, produced 52 generations, is characteristic of prolific and fast upgrowth. IRM 2 mice are suitable for the models of acute radiation damage, spontaneous tumor and transplanting tumor. To conforming the genetic homozygosity and quality of IRM 2 mouse, we performed skin grafting test, coat color test and biochemical marker analysis. Moreover, we established RAPD fingerprinting of IRM 2 mouse, showing the genetic character of the mouse. All results of these tests demonstrated that IRM 2 inbred strain mouse is high homogenous in the genetic characteristics. We clarified the G band pattern and spontaneous aberration frequencies of IRM 2 mouse because these are important for drugs screening, radiation effect, cancer research and gene map. Some discerned points between similar banding of chromosomes were presented. The results of aberration analysis showed that break was 0.33%, acentric aberration and translocation were 0.08%. The spontaneous aberration frequencies were very low. Parameters of Organ weight, hematology and biochemistry which are very important characteristics of experimental animals are both frequently used data in experimental and required item of chronicity toxicity test. 13 serum biochemistry parameters were measured using semi auto chemistry analyzer. The peripheral blood cell count and leucocyte differential count were analyzed and the myelogram was examined on regular method. The results of these parameters are relatively stable and less difference among individual. To determine the resistance of the IRM 2 inbred strain mouse to ionizing radiation, examinations for the changes of nucleated cell count in bone marrow, DNA content of bone marrow cells, WBC in peripheral blood and CFU S were performed in IRM 2 mouse following irradiated with 4.0 Gy of 137 Cs γ rays. A declining degree of WBC, the nucleated cell count and DNA content in IRM 2 mouse after irradiating was lower but recovery was quicker than in both ICR and 615 mouse, CFU S in IRM 2 was 2 times higher than in both ICR and 615. LD50 of IRM 2 mouse toγ rays were 7.17(♂)- 7.50(♀)Gy, that is, 1.73-1.57Gy and 1.44Gy higher than those of ICR and 615(P<0.01), respectively. IRM 2 mouse possessed higher resistance to ionizing radiation than other inbred and outbred strain mouse. To establish Spontaneous and transplanting tumor model in the Radiation resistant IRM 2 inbred mouse, we performed experiments as follows: (1)The Spontaneous lymphoma tissue from IRM 2 mouse were cut into several fragments sized 2.0 mm 3 then implanted subcutaneously one IRM 2 mouse, (2) breast cancer tissues from Jin BaiⅡ mouse and T 739 lung adenocarcinoma tissues were pounded and suspended in physiological saline, cell suspension were of 0.2ml (1 ×10 6cells ) injected subcutaneously into IRM 2 mouse. The frequency of tumorigenesis and survival day of bearing tumor animal were examined. The spontaneous malignant lymphoma were implanted 70 times, using 968 mice, the T 739 lung adenocarcinom were implanted 45 times .using245 mice, the breast cancer were implanted 5 times ,using 50 mice, The frequencies of tumorigenesis were 100 % for all three types of tumor, The average survival day of animal bearing lymphoma ,T 739 lung adenocarcinoma, and breast cancer were 26.0±1.6, 21.1±1.9 and 25.5± 2.8d, respectively. The results shown that tumor models established in IRM 2 inbred mouse are steady.

摘要: Many diseases such as cardiovascular disease, obesity, and diabetes are related with multi gene mutation. Multi gene interaction also plays a key role in the development of hyperlipidemia and atherosclerosis. Apolipoprotein E (apoE), a high affinity ligand of low density lipoprotein receptor (LDLR), mediates the clearance of the lipoprotein in vivo. OB R is the receptor of leptin, which can regulate the expenditure of energy and food intake. It has five spliced isoforms, the common two of which is the long form, OB Rb and the short form, OB Ra, the long receptor OB Rb has the capacity of signal transduction. The focus of the present study is to construct a multi gene mutation mouse model to characterize the mechanism of hyperlipidemia and atherosclerosis development based on the above three single gene mutation models (apoE -/- ,LDLR -/- ,and db/db mice). The results show that when with normal diet single mutation and multi gene mutation mice have a greatly elevated cholesterol and triglyceride level with progress of time, Plasma glucose level is significantly increased in the multi gene mutation mice and OB Rdb mice, While others have no distinct increase compared with wild type mice, and when with high fat diet, all the three plasma levels in the mutation mouse models especially in the multi gene mutation mice are improved remarkably in time of only two weeks, thereafter the intima of the aorta appears with typical pathological plaques. Take together, our data suggested such multi gene mutation were highly correlated with hyperlipidemia and even the process of atherosclerosis. The multi gene mutation mouse model also provides a more resemble human disease studying model, which can be very helpful to further study of pharmaceutical and gene mediated therapy.