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The Scid Congenic Inbred Department Of Breeding And Biological Characteristics Of 615-scid Mice With The Initial Application

Posted on:2005-11-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:H F ZhuFull Text:PDF
GTID:1114360185468618Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
The severe combined immunodeficiency mice (SCID) are of inability to rearrange correctly their immunoglobulin and T-cell receptor genes because of the homozygous scid mutation on chromosome 16 which result in DNA repair defect. For this reason, SCID mice are quite useful for the growth of human normal tissue and tumor cells. SCID mice are also reported as an animal model for human immune deficiency, as the ORF of the murine DNA-dependent protein kinase catalytic subunit (DNA-PKcs) gene responsible for scid gene had 78.9% homology with human DNA-PKcs gene. To bread a new severe combined immunodeficiency 615-SCID mouse with 615 genetic backgroud, we transferred the scid mutant gene of SCID mouse into 615 inbred strain with crossbackcross method. The new established 615-SCID mouse with the same brown hair as its parent mouse 615, is homozygous for the scid mutant gene lacking functional T and B lymphocyte. The conspicuous histological character of the 615-SCID mouse was observed. The total leukocyte count of the peripheral cavity of 615-SCID varied from 1500 to 4500/ul. The proportion of lymphocytes was below 30%. The proportion of B(CD19) and T(CD3, CD4, CD8) lymphocytes in the peripheral blood were both similar to SCID, But the proportion of T cell was less than SCID mouse (P<0.05 = . ELISA-test found that the level of the serum IgG was less than 0.02mg/ml. The thymus glands were very small, usually comprising one or two lobules and occasionally undetectable grossly. No lymphocytic cortex was evident in thymus. The spleen varied in size that was smaller than SCID mouse. The splenic folliculi were virtually absent. And lymphnods had only cortex. Further analysis showed that 615-SCID mouse lacking detectable T and B cells had an increased sensitivity to radiation. Most of 615-SCID could not survive when exposed to 300cGy of 137Cs γ-radiation.We transplanted human lung cancer cell line A549 and leukemia cell lines (K562 and HL-60) into 615-SCID mice in order to find the growth ability and metastasis of these cells in vivo. The results from human lung adenocarcinoma A549/615-SCID mouse metastatic model showed that the 615-SCID mouse was of more advantage in establishing metastatic...
Keywords/Search Tags:mice, 615-SCID, 615, SCID, human lung adenocarcinoma cell line, A549, leukemia cell line, K562, HL-60, xenograft, metastasis
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