Navigation Links
New genetically engineered mice aid understanding of incurable neuromuscular disease
Date:4/17/2012

COLUMBIA, Mo. -- A team of scientists from the University of Missouri created a genetically modified mouse that mimics key features of Charcot-Marie-Tooth disease, an inherited neuromuscular disease affecting approximately 150,000 people in the United States.

Charcot-Marie-Tooth, or CMT, is a group of progressive disorders that affects the peripheral nervous system, the part of the nervous system that connects the brain and spinal cord to targets such as muscles. The disease largely affects the distal nerves, those running to the feet and hands, and can progress to include the legs and arms.

"Wasting and weakening of the muscles occurs because the distal nerves are either dying or not functioning properly," said Michael Garcia, study leader and associate professor of biological sciences. "The condition can be very debilitating depending on the muscles affected and the degree to which they are affected."

No cure exists for CMT, but Garcia hopes that insights gleaned from the new mouse model may aid the development of therapeutic interventions.

"By learning about the basics of disease initiation and progression, perhaps we can soon test therapeutics designed to stop or reverse the pathology," he said.

Garcia and colleagues created the mouse model by inserting a mutated copy of a human gene into fertilized mouse egg cell. Similar mutations in that particular gene have been linked to a specific form of CMT, known as Type 2e, in humans. The cells were then implanted into female mice. The offspring that contained the mutated human gene were reared and observed for signs of CMT.

At four months of age, the mice developed a condition with several of the same hallmarks of humans with CMT Type 2e, including muscle wasting and weakness, foot deformities, and reduced ability to move. No significant neural problems or detachment of the nerves from the muscle was observed in the mice, which surprised the scientists.

"With such severe muscle atrophy we expected to see a loss of nerve connections on the muscles, but they are all there, and they look relatively healthy," said Garcia, who is also an investigator in the Christopher S. Bond Life Sciences Center.

The finding was also surprising since another mouse model, which also mimicked CMT type 2e, did show nerve detachment. This other mouse model, developed by a team in Canada, had a mutation in the same gene but at a different site in the genetic code. According to Garcia, the lack of nerve detachment observed in his mouse model may point to different underlying mechanisms for CMT type 2e.

In a follow-up study, Garcia and colleagues showed that the mice they engineered also developed an abnormal gait. The scientists evaluated the gait of the mice using a so-called CatWalk system, a device that uses light and a high-speed camera to capture certain dynamics of a running mouse's footfalls. Abnormal gaiting was observed as a decreased paw print overlap and increased hind limb drag on the left side of the body, the authors report in the study.

A high-stepped gait is characteristic of people with CMT. Weakness of the foot and leg muscles often results in foot drop, an inability to move the ankle and toes properly, which is compensated for by raising the foot higher.

"It's an exciting time for CMT type2e," said Garcia. "With two really good mouse models, we're now in a powerful position to begin to ask questions about how the disease initiates and how it progresses."

Findings from the studies are published in the July 1, 2011, issue of the journal Human Molecular Genetics and in the January 30, 2012, online issue of the journal Genes, Brain, and Behavior.


'/>"/>

Contact: Timothy Wall
walltj@missouri.edu
573-882-3346
University of Missouri-Columbia
Source:Eurekalert

Related biology news :

1. Novel bioreactor enhances interleukin-12 production in genetically modified tobacco plants
2. Researchers genetically link Lou Gehrigs disease in humans to dog disease
3. Scientists unlock possible aging secret in genetically altered fruit fly
4. Cats eye diseases genetically linked to diseases in humans
5. Origins of wolverine in California genetically verified
6. Weed resistance to glyphosate in genetically modified soybean cultivation in Argentina
7. Genetically corrected blood cells obtained from skin cells from Fanconi anemia patients
8. Genetically engineered mice yield clues to knocking out cancer
9. First genetically-engineered malaria vaccine to enter human trials
10. Genetically-modified mice reveal another mechanism contributing to heart failure
11. New study reveals first ever method to genetically identify all 8 tuna species
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/5/2017)... , April 5, 2017  The Allen Institute for ... Cell Explorer: a one-of-a-kind portal and dynamic digital window ... imaging data, the first application of deep learning to ... stem cell lines and a growing suite of powerful ... for these and future publicly available resources created and ...
(Date:4/3/2017)... 2017  Data captured by IsoCode, IsoPlexis ... a statistically significant association between the potency ... and objective response of cancer patients post-treatment. ... whether cancer patients will respond to CAR-T ... as to improve both pre-infusion potency testing and ...
(Date:3/29/2017)...  higi, the health IT company that operates the ... , today announced a Series B investment from ... The new investment and acquisition accelerates higi,s strategy to ... population health activities through the collection and workflow integration ... collects and secures data today on behalf of over ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... Oct. 11, 2017  VMS BioMarketing, a leading provider of ... oncology Clinical Nurse Educator (CNE) network, which will launch this ... communication among health care professionals to enhance the patient care ... staff, and other health care professionals to help women who ... ...
(Date:10/11/2017)... Bay, Florida (PRWEB) , ... October 11, 2017 ... ... and Drug Administration (FDA) has granted orphan drug designation to SBT-100, its novel ... (sdAb) for the treatment of osteosarcoma. SBT-100 is able to cross the cell ...
(Date:10/10/2017)... ... 10, 2017 , ... Dr. Bob Harman, founder and CEO of VetStem ... The event entitled “Stem Cells and Their Regenerative Powers,” was held ... Harman, DVM, MPVM was joined by two human doctors: Peter B. Hanson, M.D., Chief ...
(Date:10/10/2017)... ... 10, 2017 , ... The Pittcon Program Committee is pleased ... scientists who have made outstanding contributions to analytical chemistry and applied spectroscopy. Each ... leading conference and exposition for laboratory science, which will be held February 26-March ...
Breaking Biology Technology: