Transcript Mouse models

Mouse models in
Immunology
Animal models
• Naturally occurring or experimentally induced
animal diseases with pathological processes
sufficiently similar to those of human
diseases.
• They are used as study models for human diseases.
Experimental Animal Models
The choice of an animal depends on its suitability for
attaining a particular research goal
If large amounts of antiserum are sought,
rabbit, goat, sheep, or horse might be an appropriate
experimental animal.
If the goal is development of a protective vaccine, the animal
chosen must be susceptible can be mouse, rabbit
But if growth of the infectious agent is limited to humans
and primates, vaccine development may require the
use of
monkeys, chimpanzees, or baboons
Need for animal models
• In vitro assays typically rely on simple
interactions of chemicals with a drug target,
such as receptor binding or enzyme activity
inhibition.
• However, in vitro results often poorly correlate
with in vivo results because the complicated
physiological environment is absent in the in
vitro testing system.
Why mouse preferred?
• The closest to humans –
• mammal
• we share virtually ALL of our genes and use them in similar
ways
•
•
The most complex integration of systems (endocrine, immune, nervous etc.)
• ability to quickly multiply, reproducing as often as every nine
weeks. generation time is ~ 3 months, so genetics can be done
• Easy to handle
• mice are ~ 3 inches long, can keep many mice in a room.
types
• Athymic (Nude) Mice (weak T-cell immune
response)
• SCID Mice – Severe combined immunodeficient mice
• NOD mice
Nude Mouse
• Discovered in 1962.
• Is hairless, and more
importantly, lacks a
thymus.
• A genetic trait
designated nu, which is
controlled by a
recessive gene on
chromosome 11, was
discovered in certain
mice
• Mice homozygous for
this trait (nu/nu) are
hairless and have a
vestigial thymus
• NO thymus –no T-cell response and antibodies
• Immunodeficient since it can’t produce T-cells
and lymphocytes.
• USES
• This allows for implantation of human tumor cells
into mouse without rejection.
• Because they can permanently tolerate both
allografts and xenografts, they have a number of
practical experimental uses
SCID mice
• Discovered in 1983.
• S.C.I.D. – Severe combined immune deficiency
• Found to be more immunodeficient than nude
mice
• Used as a blank slate immune system.
• Used in oncology, immunology, infectious
disease, rejection of tissue transplants.
• Mice homozygous for the scid mutation (scid mice) are
severely deficient in functional B and T lymphocytes.
• Why?
• The mutation appears to impair the recombination of
antigen receptor genes and
• thereby causes an arrest in the early development of B and
T lineage-committed cells; other hematopoietic cell types
appear to develop and function normally.
• The absence of functional T and B cells enables these mice
to accept foreign cells and grafts from other strains of mice
or even from other species
• can be turned into a model of the human immune
system when injected with human cells or tissues.”
• Valuable tool to study immunodeficiency and
differentiation process of bone marrow stem cells
• CARE!
• SCID mice must be housed in a sterile (germ-free)
environment, because they cannot fight off
microorganisms of even low pathogenecity
Experimental autoimmune
encephalomyelitis (EAE) model
• is another animal model that has greatly
improved understanding of autoimmunity
• This is one of the best-studied models of
autoimmune disease
• is an animal model of brain inflammation
• It is an inflammatory demyelinating disease of
the central nervous system (CNS)
• Similar to MS
• EAE is mediated solely
by T cells and
• Demyelination is produced by injection of
– brain extracts
– CNS proteins (such as myelin basic protein)
– or peptides from such protein emulsified in an
adjuvant such as complete Freund's adjuvant
– Within 2–3 weeks the animals develop cellular
infiltration of the myelin sheaths of the central
nervous system, resulting in demyelination and
paralysis
• The presence of the adjuvant allows the generation of
inflammatory responses to the protein/peptides