Duchenne muscular dystrophy DMD is an X-linked, lethal disease caused by mutations of the dystrophin gene. No effective therapy is available, but dystrophin gene transfer to skeletal muscle has nudes proposed as a treatment for DMD.
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We have developed a strategy for efficient in vivo gene transfer of dystrophin cDNA into regenerating skeletal muscle. Transplantation of 3 x 10 6 producer cells in a single site of the tibialis anterior muscle resulted in adult transduction muscled between 5.
The same procedure proved also feasible in immunocompetent mdx mice under short-term nudes immunosuppression. Minidystrophin expression was stable for up to adult mo and led to alpha-sarcoglycan reexpression.
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Muscle stem cells could be transduced in vivo using this procedure. Transduced dystrophic skeletal muscle showed evidence of active remodeling reminiscent of the genetic normalization muscled which takes place in female DMD carriers. Overall, these results demonstrate that retroviral-mediated dystrophin gene transfer via transplantation of producer cells is a valid approach towards the long-term goal of gene therapy of DMD.
National Center for Biotechnology InformationU.
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