The absence of dystrophin at the muscle membrane leads to Duchenne muscular dystrophy (DMD), a severe muscle-wasting disease that is inevitably fatal in early adulthood. In contrast, dystrophin-deficient mdx mice appear physically normal despite their underlying muscle pathology. We describe mice deficient for both dystrophin and the dystrophin-related protein utrophin. These mice show many signs typical of DMD in humans: they show severe progressive muscular dystrophy that results in premature death, they have ultrastructural neuromuscular and myotendinous junction abnormalities, and they aberrantly coexpress myosin heavy chain isoforms within a fiber. The data suggest that utrophin and dystrophin have complementing roles in normal functional or developmental pathways in muscle. Detailed study of these mice should provide novel insights into the pathogenesis of DMD and provide an improved model for rapid evaluation of gene therapy strategies.

Cell therapy for degenerative muscle diseases such as the muscular dystrophies requires a source of cells with the capacity to participate in the formation of new muscle fibers. We investigated the myogenic potential of human fetal mesenchymal stem cells (hfMSCs) using a variety of stimuli. The use of 5-azacytidine or steroids did not produce skeletal muscle differentiation, whereas myoblast-conditioned medium resulted in only 1%-2% of hfMSCs undergoing muscle differentiation. However, in the presence of galectin-1, 66.1% ؎ 5.7% of hfMSCs, but not adult bone marrowderived mesenchymal stem cells, assumed a muscle phenotype, forming long, multinucleated fibers expressing both desmin and sarcomeric myosin via activation of muscle regulatory factors. Continuous exposure to galectin-1 resulted in more efficient muscle differentiation than pulsed exposure (62.3% vs. 39.1%; p < .001). When transplanted into regenerating murine muscle, galectin-1-exposed hfMSCs formed fourfold more human muscle fibers than nonstimulated hfMSCs (p ‫؍‬ .008), with similar results obtained in a scid/mdx dystrophic mouse model. These data suggest that hfMSCs readily undergo muscle differentiation in response to galectin-1 through a stepwise progression similar to that which occurs during embryonic myogenesis. The high degree of myogenic conversion achieved by this method has relevance for the development of therapies for muscular dystrophies.

The mdx mouse, although a genetic and biochemical homologue of human Duchenne muscular dystrophy (DMD), presents a comparatively mild histopathological and clinical phenotype. These differences are partially attributable to the greater efficacy of regeneration in the mdx mouse than in DMD muscle. To lessen this disparity, we have used a single dose of X-irradiation (16 Gy) to inhibit regeneration in one leg of mdx mice. The result is an almost complete block of muscle fiber regeneration leading to progressive loss of muscle fibers and their replacement by loose connective tissue. Surviving fibers are mainly peripherally nucleated and, surprisingly, of large diameter. Thus, X-irradiation converts mdx muscle to a model system in which the degenerative process can be studied in isolation from the complicating effect of myofiber regeneration. This system should be of use for testing methods of alleviating the myofiber degeneration which is common to mdx and DMD.

In response to a government report, which recommended a substantial increase in the number of medical students in the United Kingdom by 2005, several new medical schools have been set up throughout the country. One such school, the Brighton and Sussex Medical School (BSMS), recently opened its doors to new students. BSMS offers a 5-year medical curriculum that uses an integrated systems-based approach to cultivate academic knowledge and clinical experience. Anatomy is one of the core elements of the program and, as such, features strongly within the modular curriculum. The challenge for the anatomy faculty has been to decide how best to integrate anatomy into the new curriculum and what teaching modalities should be used. A multidisciplinary approach has been taken using both traditional and contemporary teaching methods. Unlike most of the other new medical schools, BSMS uses cadaveric dissection as the cornerstone of its teaching, as the faculty believes that dissection still provides the most powerful technique for demonstrating anatomy as well as enhancing communication and teamwork skills. The dissection experience is handled using an understanding and professional way. However, to ensure that our students do not become detached from the process of patient-focused care, emphasis in the dissecting room environment is also placed on respect and compassion. To enhance conceptual understanding of structure and function and provide further clinical relevance, we are using imaging technology to demonstrate living anatomy. Unique to the BSMS curriculum is the teaching of the anatomy in the later years of the program. During specialist rotations, students will return to the dissecting room to study the anatomy relevant to that area. Such vertical integration ensures that core anatomical knowledge is gained at the most appropriate level relative to a student's clinical experience. Anat Rec (Part B: New Anat) 284B:22-27, 2005.

Since its discovery four decades ago, the satellite cell of skeletal muscle has been implicated as the major source of myogenic cells involved in growth and repair of muscle fibres. This review not only looks at the role of the satellite cell in these processes but discusses how cells derived from other sources and tissues have recently been implicated in muscle formation and regeneration. Muscle itself also yields cells that contribute to other cell lineages although it is currently debated as to whether these cells originate within muscle or have migrated there from other tissues. The reality of using cells from muscle or other tissues to repair diseased muscle fibres is also addressed.