Muscular dystrophy (MD) is the most common genetic lethal disorder in children. Mutations in dystrophin trigger the most common form of MD, Duchenne, and its allelic variant Becker MD. Utrophin is the closest homologue and has been shown to compensate for the loss of dystrophin in human disease animal models. However, the structural and functional similarities and differences between utrophin a...

In this study, we have sought to determine whether utrophin transcripts are targeted to a distinct subcellular compartment in skeletal muscle cells, and have examined the role of the 3' untranslated region (UTR) in regulating the stability and localization of utrophin transcripts. Our results show that utrophin transcripts associate preferentially with cytoskeleton-bound polysomes via actin mic...

Utrophin is a ubiquitously expressed cytoskeletal protein which is an important structural component of the mammalian neuromuscular junction. It shows extensive sequence similarity to dystrophin leading to postulation that utrophin may be able to compensate for the absence of dystrophin in Duchenne muscular dystrophy (DMD) patients. In order to study the transcriptional control of utrophin expr...

Utrophin levels have recently been shown to be more abundant in slow vs. fast muscles, but the nature of the molecular events underlying this difference remains to be fully elucidated. Here, we determined whether this difference is due to the expression of utrophin A or B, and examined whether transcriptional regulatory mechanisms are also involved. Immunofluorescence experiments revealed that ...

To determine whether muscle satellite cells and utrophin are correlated with the degree of damage in mdx skeletal muscles, we measured the area of the degenerative region as an indicator of myofiber degeneration in the masseter, gastrocnemius, soleus, and diaphragm muscles of mdx mice. Furthermore, we analyzed the expression levels of the paired box homeotic gene 7 (pax7), m-cadherin (the maker...

The Rho family of small GTPases are signalling molecules involved in cytoskeleton remodelling and gene transcription. Their activities are important for many cellular processes, including myogenesis. In particular, RhoA positively regulates skeletal-muscle differentiation. We report in the present study that the active form of RhoA increases the expression of utrophin, the autosomal homologue o...

We examined whether calcineurin-NFAT (nuclear factors of activated T cells) signaling plays a role in specifically directing the expression of utrophin in the synaptic compartment of muscle fibers. Immunofluorescence experiments revealed the accumulation of components of the calcineurin-NFAT signaling cascade within the postsynaptic membrane domain of the neuromuscular junction. RT-PCR analysis...

Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by dystrophin deficiency. In normal muscle, dystrophin helps maintain sarcolemmal stability. Dystrophin also recruits neuronal nitric oxide synthase (nNOS) to the sarcolemma. Failure to anchor nNOS to the membrane leads to functional ischemia and aggravates muscle disease in DMD. Over the past two decades, a great variety of th...

BACKGROUND Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne Muscular Dystrophy (DMD) locus. Its regulation is of therapeutic interest as its overexpression can compensate for dystrophin's absence in animal models of DMD. The tissue distribution and transcriptional regulation of utrophin have been characterized extensively, and more recently translational control mech...

Utrophin is a large protein which accumulates at the neuromuscular synapse and myotendinous junctions in adult skeletal muscle, and is widely expressed in several non-skeletal muscle tissues. Evidence from a variety of sources suggests that a successful strategy for treatment of Duchenne muscular dystrophy patients will be to increase expression of utrophin in muscle. There is still much to be ...