Scid mice

severe combined immunodeficiency mice

1. SCID MICE PRATHYUSHA S 2 Msc BIOTECHNOLOGY

2. SCID MICE Melvin and Gayle Bosma,1983. Autosomal recessive mutation in mice. Severe deficiency in mature lymphocytes. SCID ~ human severe combined immunodeficiency. Early B & T cells lineage. Virtual absence of lymphoid cells in the thymus, spleen, lymph nodes & gut tissues-the usual locations of functional T&B cells. Precursor T&B cells-unable to differentiate into mature functional B&T lymphocytes.

3. SCID mice can neither make antibody nor carry out delayed-type hypersensitivity(DTH) or graft rejection reactions. Clean environment, succumb into early infection. Cells other than lymphocytes develop normally in mice ; RBC’s, monocytes and granulocytes . More recently, immunodeficient SCID-like mice have been developed by deletion of recombinant activating enzymes like RAG1 & RAG2. RAG knockout mice exhibit defects in both T & B cells; neither cell type can rearrange their genes for the receptor and thus neither proceeds along a normal developmental path. Immunologically competent; by transplantation of stem cells from normal mice .

4. LIMITATIONS Mutation in DNA protein kinase (prkdc gene). Leaky mutation because a certain no: of mice do produce immunoglobulin. By 10-14 months of age, virtually all SCID mice are leaky. Half of this leaky SCID mice can reject skin allogafts. Defective enzyme can function partly in T & B cell development, allowing normal differentiation of a small percentage of precursor cells .

5. Two major limitations have precluded the widespread use of the hu -SRC-SCID model system. First , the engraftment levels of human cells are low, representing only 0.5%-5% of the total SCID recipient marrow population. Second, human stem cells cannot utilize many of the murine hemopoietic growth factors produced by their hosts due to the lack of species cross-reactivity of these cytokines. This results in a cytokine-deficient microenvironment that fails to support human stem cell proliferation and differentiation.

6. TRIPLE CHIMERIC (TRIMERA) MICE Lethally irradiated normal (immunocompetent) mice transplanted with SCID marrow, followed later by a large dose of human bone marrow, resulted in low levels of human cell engraftment. This model has been used to study human stem cell phenotype and differentiation as well as the growth of human leukaemia's and lymphomas in vivo. However, in these irradiated, SCID marrow-engrafted, human marrow-injected mice, the role of natural antibodies derived from the irradiated immunocompetent host remains a potential obstacle.

7. APPLICATIONS Extremely useful in studies of cellular immunology. Graft rejection mechanisms do not operate, the SCID mice can be used for studies on cells or organs from various sources. They also support the growth of allogeneic and xenogeneic tumours. Thus, SCID mice are of interest for studies of both normal and abnormal lymphocyte development and function. In addition, they can be used to study the function of non-lymphoid cell types in the absence of lymphocytes.

8. A GOOD EXAMPLE Immune precursor cells from human sources. Re-establish SCID’s immune system. Human cells can develop into normal fashion. As a result SCID mice circulation will contain immunoglobulin of human origin. SCID mice are infected with HIV-1. SCID mice reconstituted with human lymphoid tissue provides an animal model in which to test therapeutics or prophylactic strategies against HIV infection of the transplanted human lymphoid tissue.

9. B U B B L E B O Y

10. REFERENCES KUBY,Immunology,6 th ed http://onlinelibrary.wiley.com www.genecards.com

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