Experimenting on Human cells

Mice are a commonly used tool to study autoimmunity but it would be better to study human immune cells. 

Enter the NOG mouse.
NOG History.png
The NOD obese diabetic mouse was a mouse strain that was developed in Japan and spontaneously develops diabetes. 

It can be used of EAE studies too but it isrelatively EAE resistant due to genes on chromosome 7.

Baker D, Rosenwasser OA, O'Neill JK, Turk JL Genetic analysis of experimental allergic encephalomyelitis in mice. J Immunol. 1995;155:4046-51.


The SCID severe combined immunodeficient mice has a defective lymphoid system and does not make T or B cells. In humans, SCID is colloquially known as "bubble boy" disease, as victims may require complete clinical isolation to prevent lethal infection from environmental microbes.

In mice the condition is due to a rare recessive mutation on Chromosome 16 responsible for deficient activity of an enzyme involved in DNA repair (Prkdc or "protein kinase, DNA activated, catalytic polypeptide"). Because V(D)J recombination does not occur, the humoral and cellular immune systems fail to mature. SCID mice, therefore, present with impaired ability to make T or B lymphocytes and cannot efficiently fight infections, nor reject tumors and transplants.

By crossing SCID mice with mice carrying mutations in related genes, such as interleukin-2 receptor gamma, more efficient immunocompromised strains can be created to further aid research.

These strains termed NOG mice can be used as an empty mouse to repopulate with human immune cells. The problem here is they react against the mouse tissue and cause lethal graft verses host disease.

However you can take human bone marrow stem cells and transplant these into mice and with time the repopulate the mouse but learn not to reject the mouse tissue. They then have human immune cells in a mouse and now you can use them to investigate the effects of drugs that only work on human cells.
Can we get EAE in these mice? It is only a matter of time before this happens. New versions have been made that have human major histocompatibility complex and so will make immune recognition  even better.

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