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Human Molecular Genetics, 2000, Vol. 9, No. 12 1843-1852
© 2000 Oxford University Press

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

Y. Torrente1, M.G. D’Angelo2, Z. Li4, R. Del Bo3, S. Corti2, M. Mericskay4, A. DeLiso2, A. Fassati5, D. Paulin4, G.P. Comi1,2, G. Scarlato1,2 and N. Bresolin,1,2,+

1IRCCS Ospedale Maggiore Policlinico, Milan, Italy, 2Centro Dino Ferrari, Institute of Clinical Neurology, University of Milan, Milan, Italy, 3IRCCS Eugenio Medea, Bosisio Parini, Italy, 4Université Paris 7, Case 7136, 2 place Jussieu, 75251 Paris, France and 5Wohl Virion Centre, Windeyer Institute, University College London, 46 Cleveland Street, London W1P 6BD, UK

Duchenne muscular dystrophy (DMD) is a lethal recessive disease caused by the absence of dystrophin 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 dystrophin deficiency based on the transplantation of normal somite-derived cells into mdx mouse embryos. Somite-derived cells were isolated from E11.5 transgenic mouse embryos expressing the LacZ gene under the control of the muscle-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 were able to cross the placenta and migrate into host embryonic tissues. The pattern of donor cell distribution in host tissues depended on the gestational age of the transplanted embryos. Cells were found in hindlimb muscles, diaphragm, heart and ribs in E11.5 treated embryos and in the skull, ribs, vertebrae 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 quadriceps muscle fibres and in 4% of heart myocytes of two of seven 8-week-old treated mdx mice.

+ To whom correspondence should be addressed at: Institute of Clinical Neurology, University of Milan, Padiglione Ponti, Ospedale Policlinico, via Francesco Sforza 35, 20122 Milan, Italy. Tel: +39 02 5503 3817; Fax: +39 02 5519 0392; Email: gpcomi@unimi.it


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