MDX MOUSE肌营养不良实验鼠课件.ppt

The treatment of muscular dystrophy (1) The treatment of pharmaceuticals (2) Gene therapy (3) Cell transplantation therapy [Mesenchymal Stem Cell Transplant to Treat Duchenne Muscular Dystrophy ] The mdx mouse——肌营养不良实验鼠 These dystrophic mice have a point mutation that exchanged the base cytosine (C) in position 3,185 in exon 23 against a thymine (T). This converted the CAA codon, which normally codes for the amino acid glutamine, to the triplet TAA (in the mRNA it become UAA) which is a premature stop codon. 它是一种点突变实验鼠，基因突变发生在肌营养不良蛋白23号外显子的第3185号核苷酸上，将本该编码为谷氨酸盐氨基酸的CAA码，改变成了TAA码，这是一个停止合成蛋白质的密码，造成了点突变，使得翻译蛋白质的过程提前停止. The treatment of pharmaceuticals Studies on mdx mice have turned up one drug-an antibiotic called gentamicin(正大霉素) that causes the animals to synthesize dystrophin and protects them from muscle damage. Gentamicin cure in mdx mice Gentamicin is an antibiotic that causes the RNA translation mechanism in the ribosomes to ignore such a prema-ture stop codon, i.e. to read through it and produce a dystrophin molecule . Gentamicin injections into mdx mice led to the appearance of new dystrophin in up to 20% of the muscle fibers. And mice with this amount of dystrophin had ameliorated改善的 clinical symptoms.  Gentamicin cure in humen About 5% to 10% of Duchenne boys have a point mutation in their dystrophin gene which changed an amino acid code word into one of the three stop codons. In the mRNA, these codons become UGA, UAG, and UAA and cause the protein synthesis to shut down prematurely, before the new protein, in this case dystrophin, is ready. So ,we can use the same method to cure the muscular dystrophy in human being. Other discovery about this drug The researchers analyzed and discovered that gentamicin exists in 5 varieties with different structures. Although they all had the same antibiotic activity, their read through efficiency was quite distinct and their toxicity also. This means that gentamicin preparations would have to be carefu