Immunohistochemical studies show truncated dystrophins in the myotubes of three fetuses at risk for Duchenne muscular dystrophy.

Abstract

We have performed immunohistochemical studies on muscle tissue of three 12 week old fetuses at risk for DMD, using antisera directed against regions located NH2-proximally and centrally in the rod shaped spectrin-like domain and against the COOH-terminus of dystrophin. All three fetuses had a family history ofDMD. Truncateddystrophins were identified in all three cases by a positive reaction with the NH2-proximal antibody, different reactions with the central antibody, and a negative reaction with the COOH-terminal antibody. These data indicate that a panel of antibodies would, in principle, permit 'immunological' mapping of dystrophin mutations. This is diagnostically important in the 35% of families where no mutation is detectable at the DNA level. Secondly, by using this mapping technique it may also become possible to identify the at risk haplotype when DNA analysis is not informative. This may be of great value in DMD carrier detection.X linked Duchenne muscular dystrophy (DMD) is the most common of all severe muscular dystrophies

Dystrophin expression in the developing conduction system of the human heart

“…At early fetal stages dystrophin was detected in atrial cardiomyocytes and in the specialized cardiomyocytes that constitute the conduction system of the ventricle. In the heart of a 12-week-old DMD fetus (Ginjaar et al, 1991) dystrophin could not be detected.…”

“…Interestingly, at this stage it is now predominantly found in the sarcolemma of the myocytes of the His-bundle ( Fig. 6 0 . In the heart of a fetus of 12 weeks of development found to be affected with DMD (family 2, Ginjaar et al, 1991), a-MHC is observed in the bundle branches (Fig. 7A), whereas dystrophin is absent in these cardiomyocytes (Fig.…”

The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy

“…The symptoms worsened over time, suggesting that the 70–80‐kDa dystrophin was unable to restore sarcolemmal stability. In a separate study, immunohistochemical assays revealed expression of truncated dystrophin in myotubes isolated from three 12‐week‐old aborted fetuses at risk for DMD, suggesting that mutant dystrophin is synthesized in human DMD patients . Recently, the truncated form of dystrophin was detected within the ER/Golgi compartments of mdx mice , suggesting that the 115‐kDa dystrophin may be retained in the ER/Golgi compartments.…”

“…However, dystrophin mRNA levels vary widely, depending on the causative mutation in human DMD and Becker muscular dystrophy patients . It was previously thought that the 115 kDa dystrophin protein is rapidly degraded after synthesis in mdx muscle, but studies suggest that truncated dystrophin may be expressed at the sarcolemma or retained in the ER/Golgi .…”