New mouse model provides insight into human neuronal diseases

May 26 2009

Neurosensory diseases are difficult to model in mice because their symptoms are complex and diverse. The genetic causes identified are often lethal when transferred to a mouse.

The lack of animal models slows progress in understanding and treating the diseases. By strategically altering a protein-making molecule, a mouse was made to help understand nervous system diseases that impair feeling and cause paralysis of the arms and legs in humans.

Scientists have created a mouse to help understand human neuronal diseases that impair a patient's ability to feel and to move their arms and legs. By strategically altering a protein-making molecule, a mouse was made with symptoms similar to the nervous system diseases, Charcot-Marie-Tooth (CMT) and hereditary motor neuropathy (HMN). In CMT and HMN, neurons that signal and maintain muscle cells become defective, which causes weakening and loss of muscle that is significant enough in some cases to lead to death. The symptoms become progressively worse over time and no effective treatments or cures exist for these diseases. Researchers came together from the University College London (UCL), the Medical Research Centre (MRC) Harwell, the University of Oxford, and the University of London in England, Vrije University in The Netherlands and Jackson Laboratories in the US to make a genetic change in mice that has been associated with CMT and HMN diseases in people.

Neurosensory diseases are difficult to model in mice because they involve symptoms that are complex and diverse. These diseases are passed from parents to their children but the genetic causes identified are often lethal when transferred to a mouse. The lack of animal models slows progress in understanding and treating the diseases.

The researchers made a mutation in a protein, which is part of the protein building machinery, called glycyl-tRNA synthetase (GARS). As described in their study in Disease Models & Mechanisms (DMM), mice with mutations in the GARS gene have some of the same symptoms as CMT and HMN patients. Their hope is that this mouse can be used to study what causes these diseases and how it might effectively be treated. Mice with defects in some of this protein have problem with grip strength and motor skills while symptoms are more pronounced in animals that carry the mutation in all of their protein copies. This report is the first documentation of successful breeding of animals with this mutation, giving researchers access to new materials to understand how this gene influences human neuronal diseases.

When the researchers made the same mutation in two different breeds of mice it caused two distinguishable sets of symptoms, demonstrating that the genetic background influences the effects of the GARS gene mutation. This variability in the mouse disease symptoms is also seen in humans, and may help shed light on how CMT and HMN differently affect individual patients' symptoms.