Transplacental injection of somite-derived cells in mdx mouse embryos for the correction of dystrophin deficiency

Duchenne muscular dystrophy (DMD) is a lethal recessive disease caused dyst rophin in skeletal muscle, heart and other tissues. No cure is available at present for DMD, Here we describe a new strategy for the correction of dys trophin deficiency based on the transplantation of normal somite-derived ce lls into mdx mouse embryos. Somite-derived cells were isolated from E11.5 t ransgenic mouse embryos expressing the LacZ gene under the control of the m uscle-specific desmin promoter and injected into the uterine circulation of pregnant mdx mice at gestational days E11.5-E17. Approximately 30% of the injected mdx embryos survived the procedure. Donor somite-derived cells wer e able to cross the placenta and migrate into host embryonic tissues. The p attern of donor cell distribution in host tissues depended on the gestation al age of the transplanted embryos. Cells were found in hindlimb muscles, d iaphragm, heart and ribs in E11.5 treated embryos and in the skull, ribs, v ertebrae and lung of E15-E17 treated embryos. Normal dystrophin transcripts were detected in muscle and bone by RT-PCR, Histochemical analysis showed co-localization of LacZ and dystrophin expression in 5% of soleus and quadr iceps muscle fibres and in 4% of heart myocytes of two of seven 8-week-old treated mdx mice.