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:11/20/2018)... SAN FRANCISCO (PRWEB) , ... November 19, 2018 , ... ... plant growing system for the home, today announced a discount of $420 for its ... off the $2690 GroBox if paid in full, with other discount and payment options ...
(Date:11/20/2018)... ... ... Thanks to its long-standing expertise in ID reader development and industrialization, Elyctis ... company now proposes a full range of readers able to satisfy all needs including ... used by professionals either in a fixed location or on the move as well ...
(Date:11/16/2018)... ... November 16, 2018 , ... Bergeson ... Things Chemical™ and it will engage listeners in intelligent, insightful conversation about everything ... surrounding chemicals. B&C’s talented team of lawyers, scientists, and consultants will keep listeners ...
Breaking Biology News(10 mins):
(Date:12/5/2018)... ... December 05, 2018 , ... Leading authority on how to bridge ... with his “The Referral Playbook: How to Increase Sales with Proven Networking Strategies.” ... will go to the Alzheimer’s Foundation of America (AFA). , Itzkowich is hosting ...
(Date:11/28/2018)... ... November 28, 2018 , ... Earlier this month, Lajollacooks4u's Founder and Chef ... experience the height of truffle season. , Her first stop was Umbria, ... in the exclusive Black Truffle Lodge in the small mountain village of Pettino, Chef ...
(Date:11/20/2018)... ... November 20, 2018 , ... Each year Forbes receives thousands of ... which highlights outstanding performance by individuals under 30 years of age. The Forbes 30 ... from Sports and Entertainment to Venture Capital and Science. , In 2017, Visikol ...
(Date:11/13/2018)... Springs, GA (PRWEB) , ... November 12, 2018 ... ... dentist with state-of-the-art practices in Alpharetta and Sandy Springs, now welcomes new ... aligners provide a discreet and comfortable alternative to traditional braces in the Sandy ...
Breaking Biology Technology: