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Canine and feline models of human inherited muscle diseases.
Shelton GD, Engvall E
Neuromuscul Disord. 2005 Feb;15(2):127-38
Elimination of myostatin does not combat muscular dystrophy in dy mice but increases postnatal lethality.
Li ZF, Shelton GD, Engvall E
Am J Pathol. 2005 Feb;166(2):491-7
The new frontier in muscular dystrophy research: booster genes.
Engvall E, Wewer UM
FASEB J. 2003 Sep;17(12):1579-84
Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice.
Guo LT, Zhang XU, Kuang W, Xu H, Liu LA, Vilquin JT, Miyagoe-Suzuki Y, Takeda S, Ruegg MA, Wewer UM, Engvall E
Neuromuscul Disord. 2003 Mar;13(3):207-15
ADAM12 alleviates the skeletal muscle pathology in mdx dystrophic mice.
Kronqvist P, Kawaguchi N, Albrechtsen R, Xu X, Schrøder HD, Moghadaszadeh B, Nielsen FC, Fröhlich C, Engvall E, Wewer UM
Am J Pathol. 2002 Nov;161(5):1535-40
Eva Engvall's Research Focus
Skeletal muscle makes up a major portion of the human body and is essential for life. Loss of skeletal muscle is a chronic problem in aging and an acute problem in muscular dystrophy and other diseases such as cancer. Muscle diseases occur not only in humans but also in other species such as dogs, cats, and mice. There has been tremendous progress in the diagnosis of muscular dystrophy. Although currently there are few available effective treatments for muscle loss in muscular dystrophy and aging, multiple approaches to reduce muscle degeneration and to promote muscle regeneration are being tested experimentally. Dr. Engvall’s laboratory is exploring the use of differentiation factors for muscle regeneration and the use of myogenic cells from non-muscle tissues for muscle cell replacement.
Eva Engvall's Research Report
Basement Membranes: Structure and Function in Development, Regeneration, and Cancer
Our research centers on the role of extracellular matrix in cell differentiation. The current focus is on development and regeneration of muscle and nerve.
Muscle normally has a large capacity for regeneration, which involves activation and proliferation of muscle stem cells and their differentiation into functional muscle fibers. Muscular dystrophy is a group of rare genetic diseases characterized by degeneration and loss of function of skeletal muscle. Thus, in muscular dystrophy and other muscle diseases, and even in normal aging, regeneration is insufficient to compensate for degeneration. Our hypothesis is that the proteins mutated in the muscular dystrophies are among the ones most critical for regeneration. We have generated a mouse model for merosin (laminin alpha -2)-deficient congenital muscular dystrophy by ablating the lama2 gene through the insertion of a reporter gene, lacZ. Homozygous mutant mice develop an early, lethal form of muscular dystrophy. By monitoring b-galactosidase activity during muscle development and regeneration, we determined that the lama2 gene was active in mononucleated myoblasts but inactive in the differentiated, multinucleated myotubes. In contrast, the protein is deposited around the myotubes. Stem cells are activated and proliferate in the absence of laminin alpha -2, but very few myotubes form,. The myotubes that do form can not complete maturation into functional muscle. We conclude that laminin alpha -2 is most essential for late stages of muscle regeneration.
Additional factors are important for regeneration of striated muscle, including stem cells. We currently study the muscle-specific sarcoglycan genes as well as the muscle specific caveolin, caveolin-3. Sarcoglycans and caveolin-3 are mutated in particular forms of limb-girdle muscular dystrophy. In collaboration with Drs. Millan and Stallcup, we aim to identify mesenchymal stem cells that may be recruited and used as an alternative source of cells for muscle regeneration in situations where the resident stem cell pool in muscle has been depleted.
About Eva Engvall
Eva Engvall earned her Ph.D. from the University of Stockholm in 1975. Her postdoctoral work was done at the University of Helsinki and City of Hope National Medical Center in California, where she was subsequently appointed to staff. Dr. Engvall was recruited to Sanford-Burnham Medical Research Institute in 1979. For 1994-1996, Dr. Engvall held joint appointments at this institute and as Chairperson of the Department of Developmental Biology at Stockholm University. Dr. Engvall's work on the development of the Enzyme Linked Immunosorbent Assay, ELISA, has been widely acclaimed, including honors from The German Society for Clinical Chemistry, the U.S. Clinical Ligand Assay Society, and in 1995, a special award from the Ed and Mary Shea Family Foundation. Dr. Engvall received an honorary degree in Medicine from the University of Copenhagen in November 1994.