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 ModelsThe choice of an animal depends on its suitability for attaining a

particular research goalIf 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 immuno-deficient 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 solelyby 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