A golden retriever in Brazil name Ringo is providing a new lead in research into one type of muscular dystrophy. The dog has the gene mutation for Duchenne muscular dystrophy (DMD) but has stayed healthy.
DMD is one of the most common forms of muscular dystrophy that only occurs in males. A group of golden retrievers in Brazil carry the gene mutation for DMD, which causes the loss or dysfunction of a protein called dystrophin. The dogs with the bad gene were very weak and typically died by age 2 years of age, but Ringo was able to walk and run normally and lived to the age of 11.
The study, published by the journal Cell, found the location of a protective gene that boosts muscle regeneration. This gene helps some dogs "escape" the disease's effects despite having the DMD gene mutation. The study was conducted by researchers at Boston Children's Hospital, the Broad Institute of the Massachusetts Institute of Technology, Harvard University, and the University of São Paolo in Brazil using a technique called genomic-wide association studies.
This research was possible because the entire dog genome, which is very diverse because of the many breeds of dogs, has been mapped. The team compared the genomes of two escaper dogs (Ringo and one of his male offspring) and 31 golden retrievers that were severely affected by DMD. They found that a region on one chromosome that was associated with disease severity and then narrowed that down to one gene, called Jagged1, which is known to be involved in muscle regeneration. This in turn led them to a sequence of DNA that turns Jagged1 on. As a result, the escaper dogs, which carried a slightly different sequence, expressed Jagged1 at twice the rate of the affected dogs.
To confirm this finding, the research team also studied zebra fish that have been genetically engineered to carry the DMD gene mutation. When the expression of Jagged1 was stimulated in these fish, they had normal looking muscles and swam normally.
Using these findings, researchers will be able use Jagged1 to look for treatments to improve muscle function.