Online Purchasing Account You are logged on as Guest. LoginRegister a New AccountShopping cart (Empty)
United States 

Surprise mutation to JAG1 salvages Duchenne muscular dystrophy phenotype

Muscular dystrophies are a group of inherited genetic and progressive conditions that gradually cause the muscles to weaken, leading to an increasing level of disability. Duchenne muscular dystrophy (DMD) is one of the most common and severe forms of muscular dystrophy. It is a recessive X-linked disorder affecting boys in early childhood. It has an incidence of 1 in 3,600 male infants. The condition is due to a mutation in the gene dystrophin, which codes for the protein of the same name. The latter provides stability to the dystroglycan complex of the cell membrane and as such, is a critical structural component within the muscle tissue. In its absence, calcium enters the cell membrane of each muscle fiber causing alterations to signaling pathways and absorption of water by the mitochondria, which then burst. As a result of the decrease in the mitochondrial mass, stress-induced cytosolic calcium signals and reactive oxygen species production are enhanced. It eventually leads to death of the cells by necrosis causing the early and characteristic symptoms of muscle weakness of the legs and the pelvis. As the disease progresses, this weakness spreads to the arms, the neck and other areas such as the heart and the respiratory muscles. Muscle fibers are slowly substituted with adipose and connective tissue and an overall loss of muscle mass is observed. There is, unfortunately, no cure for DMD. Current treatments such as β2-agonists, corticosteroids and physical therapy are only palliative and men with the condition can expect to live into their 20s.

Natassia M. Vieira and colleagues from Harvard Medical School and the University of Sao Paulo noticed that Ringo, a golden retriever bred to have a severe form of muscular dystrophy, did not show any signs of the disease.

Interestingly, one of his puppies also seemed to be protected. Both dogs have inherited the dystrophin mutation and were rescued by a mutation in a gene called Jagged 1 (JAG1). The latter is the ligand for the receptor Notch 1, a type 1 transmembrane protein that controls cell fate decisions and therefore plays a key role in several developmental processes. Genome-wide analysis demonstrated that the mutation was absent from severely affected dogs from the same colony. Jagged 1 expression was also found to be significantly up-regulated both at the mRNA and protein levels in the muscles of Ringo and his son when compared with affected dogs. The authors demonstrated that overexpression of Jagged 1 not only rescued dogs with a dysfunctional dystrophin but also salvaged similar dystrophic muscle phenotype in other species. Using an affected dystrophic zebrafish model, they mimicked the over-expression of Jagged 1 and noticed a protection from muscle shredding and other abnormalities typically associated with muscular dystrophy in the zebrafish. Further work was conducted on mice where injury on the muscles of the anterior legs was induced with a cardiotoxin. As a result of this toxic insult, Jagged 1 was found to be up-regulated. Finally, muscle cells are expected to divide less recurrently in dystrophic dogs than in healthy dogs. They determined that muscle cells from escaper dogs do in fact divide significantly faster than those from affected dogs. Altogether, these results demonstrate that mutations have the potential to counteract the effects of a genetic disorder and that thanks to Ringo, Jagged 1 may be an interesting and potent ally against DMD. Both Ringo and his son went on to live a normal life.

Enzo Life Sciences offers a comprehensive portfolio for molecular biology and neuroscience research including antibodies, immunoassays, live cell analysis tools and recombinant proteins, some of which are described below.

Share this TechNote

Never miss a new TechNote!

Receive our TechNotes as soon as they are published.


Follow Us!

 
comments powered by Disqus

Reference:

  1. N.M. Vieira, et al. Jagged 1 rescues the Duchenne muscular dystrophy phenotype. Cell (2015) 163: 1204.

Related Products

Osteopontin (rodent), ELISA kit 

ELISA, Colorimetric detection | Print as PDF
 
ADI-900-090A 96 wells 504.00 USD
Do you need bulk/larger quantities?
 

Osteopontin (human), ELISA kit 

ELISA, Colorimetric detection | Print as PDF
 
ADI-900-142 96 wells 499.00 USD
Do you need bulk/larger quantities?
 

Osteopontin polyclonal antibody 

IHC (PS) | Print as PDF
 
ADI-905-500-1 1 ml 333.00 USD
Do you need bulk/larger quantities?
 

Osteopontin monoclonal antibody (53) 

ELISA, IHC (FS), IHC (PS), WB | Print as PDF
 
ADI-905-629-100 100 µg 301.00 USD
Do you need bulk/larger quantities?
 

Osteopontin monoclonal antibody (87-B) 

ELISA, IHC (FS), IHC (PS), WB | Print as PDF
 
ADI-905-630-100 100 µg 281.00 USD
Do you need bulk/larger quantities?
 

Notch1 monoclonal antibody (3E12) 

WB | Print as PDF
 
ADI-905-897-100 100 µl 418.00 USD
Do you need bulk/larger quantities?
 

IMMUNOSET® Osteopontin (human), ELISA development set 

ELISA, Colorimetric detection | Print as PDF
 
ADI-960-142 10x96 wells 472.00 USD
Do you need bulk/larger quantities?
 

Cpn10 (human), (recombinant) 

Produced in E. coli., ≥90% (SDS-PAGE; Western blot), ELISA, WB | Print as PDF
 
ADI-SPP-110-D 50 µg 207.00 USD
 
ADI-SPP-110-F 200 µg 494.00 USD
Do you need bulk/larger quantities?
 

DNER (extracellular domain) (human):Fc (human), (recombinant) 

Notch ligand
Produced in HEK 293 cells. Signal peptide and extracellular domain of human DNER (aa 1-637) are fused at the C-terminus to the Fc portion of human IgG., ≥90% (SDS-PAGE) | Print as PDF
 
ALX-201-428-C010 10 µg 245.00 USD
Do you need bulk/larger quantities?
 

DLK1 (human), (recombinant) (His-tag) 

Notch ligand
Produced by HEK 293 cells. DLK1 (Ala24-Pro297) is fused at the C-terminus to a His-tag., ≥95% (SEC-HPLC and reducing SDS-PAGE) | Print as PDF
 
ALX-201-764-0010 10 µg 194.00 USD
 
ALX-201-764-0050 50 µg 499.00 USD
Do you need bulk/larger quantities?
 

DLL1 (soluble) (human), (recombinant) 

Notch ligand
Produced in HEK 293 cells. Recombinant human sDLL-1 contains 522 amino-acid residues., ≥95% (SDS-PAGE and HPLC) | Print as PDF
 
ALX-201-765-0025 25 µg 342.00 USD
Do you need bulk/larger quantities?
 

DLL4 (soluble) (human), (recombinant) 

Notch ligand
Produced in HEK 293 cells. Recombinant human sDLL-4 contains 498 amino-acid residues., ≥95% (SDS-PAGE and HPLC) | Print as PDF
 
ALX-201-766-0025 25 µg 342.00 USD
Do you need bulk/larger quantities?
 

DLL1 (human) polyclonal antibody 

ELISA, WB | Print as PDF
 
ALX-210-483-C100 100 µg 310.00 USD
Do you need bulk/larger quantities?
 

Osteopontin polyclonal antibody 

ELISA, IHC (PS), WB | Print as PDF
 
ALX-210-309-R020 20 µl 205.00 USD
 
ALX-210-309-R100 100 µl 809.00 USD
Do you need bulk/larger quantities?
 

γ-Secretase inhibitor 

≥90% | Print as PDF
 
ALX-260-127-M001 1 mg 344.00 USD
Do you need bulk/larger quantities?
 

Compound E 

γ-Secretase inhibitor
209986-17-4, ≥95% (HPLC) | Print as PDF
 
ALX-270-415-C250 250 µg 118.00 USD
 
ALX-270-415-M001 1 mg 336.00 USD
Do you need bulk/larger quantities?
 

DAPT 

γ-Secretase inhibitor
208255-80-5, ≥98% (HPLC) | Print as PDF
 
ALX-270-416-M005 5 mg 99.00 USD
 
ALX-270-416-M025 25 mg 359.00 USD
Do you need bulk/larger quantities?
 

Compound 34 

γ-Secretase inhibitor
≥98% | Print as PDF
 
ALX-270-417-C200 200 µg 82.00 USD
 
ALX-270-417-M001 1 mg 268.00 USD
Do you need bulk/larger quantities?
 

Presenilin 1 monoclonal antibody (APS 11) 

ELISA, ICC, IHC (PS), WB | Print as PDF
 
ALX-804-554-C200 200 µg 562.00 USD
Do you need bulk/larger quantities?
 

Presenilin 1 monoclonal antibody (APS 18) 

ELISA, ICC, WB | Print as PDF
 
ALX-804-555-C200 200 µg 410.00 USD
Do you need bulk/larger quantities?
 

DLK1 (mouse) monoclonal antibody (PF183E) 

ELISA, WB | Print as PDF
 
ALX-804-743-C050 50 µg 310.00 USD
 
ALX-804-743-C100 100 µg 566.00 USD
Do you need bulk/larger quantities?
 

Dishevelled-1 polyclonal antibody 

WB | Print as PDF
 
BML-DA4170-0100 100 µl 356.00 USD
Do you need bulk/larger quantities?
 

Dishevelled-3 polyclonal antibody 

WB | Print as PDF
 
BML-DA4370-0025 25 µl 100.00 USD
 
BML-DA4370-0100 100 µl 320.00 USD
Do you need bulk/larger quantities?
 

Dishevelled-2 (human) polyclonal antibody 

WB | Print as PDF
 
BML-DA4470-0025 25 µl 110.00 USD
 
BML-DA4470-0100 100 µl 345.00 USD
Do you need bulk/larger quantities?
 

Boc-Gly-Val-Val-CHO 

γ-secretase inhibitor
Synthetic., ≥98% (TLC) | Print as PDF
 
BML-PI128-0005 5 mg 115.00 USD
 
BML-PI128-0025 25 mg 417.00 USD
Do you need bulk/larger quantities?
 

ROS-ID® ROS/RNS detection kit 

Monitor  reactive oxygen species and nitrogen species in live cells
Fluorescence microscopy | Print as PDF
 
ENZ-51001-200 1 Kit 281.00 USD
Do you need bulk/larger quantities?
 

ROS-ID® Total ROS/Superoxide detection kit 

Directly Monitor Global Levels  of Reactive Oxygen Species (ROS), and Specifically Superoxide
Flow Cytometry, Fluorescence microscopy, Fluorescent detection, HTS | Print as PDF
 
ENZ-51010 1 Kit 235.00 USD
Do you need bulk/larger quantities?
 

ROS-ID® Total ROS detection kit 

Flow Cytometry, Fluorescence microscopy, Fluorescent detection, HTS | Print as PDF
 
ENZ-51011 1 Kit 172.00 USD
Do you need bulk/larger quantities?
 

ROS-ID® Superoxide detection kit 

Flow Cytometry, Fluorescence microscopy, Fluorescent detection, HTS | Print as PDF
 
ENZ-51012 1 Kit 172.00 USD
Do you need bulk/larger quantities?
 

ROS-ID® NO Detection kit 

Fluorescence microscopy, Fluorescent detection | Print as PDF
 
ENZ-51013-200 1 Kit 172.00 USD
Do you need bulk/larger quantities?
 

ROS-ID® Hypoxia/Oxidative stress detection kit 

Specific detection system for simultaneous analysis of hypoxia and oxidative stress using microscopy and flow cytometry
Flow Cytometry, Fluorescence microscopy, Fluorescent detection, HTS | Print as PDF
 
ENZ-51042-0125 125 tests 105.00 USD
 
ENZ-51042-K500 500 tests 367.00 USD
Do you need bulk/larger quantities?
 

Recommend this page

 
For Research Use Only. Not for use in diagnostic procedures.
Keep in touch

©2017 Enzo Life Sciences, Inc.,