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Science & Innovation

Science 101: The Mighty Mouse - Advanced Preclinical Models

MouseOne of the greatest lab partners science has ever known is also one of its tiniest: the mouse, which has contributed more to our understanding of how human cells and tissue function than almost any other animal. Mice and men are quite different on the surface, but genetically are very close, with an estimated 85 percent of shared working DNA.1

The ability to use genetics to create powerful mouse models has helped significantly advance our understanding of how the body works, the causes of disease as well as potential treatments, including for rare and debilitating human diseases.

In the 1980s, scientists discovered that an autosomal recessive mutation in certain mice significantly impaired their ability to generate types of white blood cells known as lymphocytes, which play several roles in the immune system.2,3 If human white blood cells, peripheral leukocytes, were injected into these severe combined immunodeficiency (SCID) mice, the mice developed active human immune systems.4

These humanized SCID mice were instrumental in early HIV research, and later developments have impacted other immune disorders, cancers and rare and genetic diseases as well as our understanding blood cell development.5 In March 2016, Jackson Laboratory (JAX) researchers used two mouse models of Charcot-Marie-Tooth type 2D (CMT2D) to determine that improving the efficacy of synaptic junctions between nerve cells may help alleviate symptoms, such as muscle weakness and fatigue, experienced by patients with this rare, genetic neurological condition.  This new finding reverses conclusions of earlier research that ascribed symptoms to degeneration of sections of nerve cells called axons.6

Today, using gene-editing techniques, scientists can make mouse models for almost any human disease. In fact, JAX alone has more than 7,000 genetically defined strains of mice.7 Small, fast reproducers and easy to handle, genetically identical mice help remove uncertainly about the accuracy or replication of experimental results due to the model system.8 Mice also offer the benefit that their years are roughly equal to 30 human years, so scientists can create life-long experiments that in humans would take decades.

In the future, mice will matter even more, as scientists seek to enhance our understanding of human disease. Our two species, though separated by some 75 million years of evolution,9 remain closely aligned.

References

  1. https://www.genome.gov/10001345
  2. http://www.ncbi.nlm.nih.gov/pubmed/6823332?dopt=Abstract
  3. http://jid.oxfordjournals.org/content/208/suppl_2/S125.full#ref-3  Introduction
  4.  http://www.ncbi.nlm.nih.gov/pubmed/2970594?dopt=Abstract
  5.  http://jid.oxfordjournals.org/content/208/suppl_2/S125.full#ref-3  Introduction
  6.  https://www.jax.org/news-and-insights/2016/march/boosting-synaptic-deficits-treats-cmt2d
  7.  https://www.jax.org/genetics-and-healthcare/genetics-and-genomics/why-mouse-genetics
  8.  https://www.jax.org/genetics-and-healthcare/genetics-and-genomics/why-mouse-genetics
  9.  https://www.genome.gov/10005831

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