SCID mice have an autosomal recessive mutation that causes severe deficiencies in mature lymphocytes. They lack functional T and B cells and have a virtual absence of lymphoid cells. As a result, SCID mice cannot make antibodies or reject transplants. While other cells develop normally, SCID mice succumb to early infections due to their lack of immune response. SCID mice have been used to study lymphocyte development and function as well as the growth of tumors. They have also been used as humanized mouse models by transplanting human immune cells, allowing the study of HIV infection in human tissues.
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.
5. 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.
6. 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.
7. 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.
8.
9. 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.
10. 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.