Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1843-1852 |
| Number of pages | 10 |
| Journal | Human Molecular Genetics |
| Volume | 9 |
| Issue number | 12 |
| Publication status | Published - 2000 |
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ASJC Scopus subject areas
- Genetics
Cite this
Transplacental injection of somite-derived cells in mdx mouse embryos for the correction of dystrophin deficiency. / Torrente, Y.; D'Angelo, M. G.; Li, Z.; Del Bo, R.; Corti, S.; Mericskay, M.; DeLiso, A.; Fassati, A.; Paulin, D.; Comi, G. P.; Scarlato, G.; Bresolin, N.
In: Human Molecular Genetics, Vol. 9, No. 12, 2000, p. 1843-1852.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transplacental injection of somite-derived cells in mdx mouse embryos for the correction of dystrophin deficiency
AU - Torrente, Y.
AU - D'Angelo, M. G.
AU - Li, Z.
AU - Del Bo, R.
AU - Corti, S.
AU - Mericskay, M.
AU - DeLiso, A.
AU - Fassati, A.
AU - Paulin, D.
AU - Comi, G. P.
AU - Scarlato, G.
AU - Bresolin, N.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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M3 - Article
C2 - 10915773
AN - SCOPUS:0033854067
VL - 9
SP - 1843
EP - 1852
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 12
ER -