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Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice.
Cell. 2010 Dec 23; 143(7):1059-71.Cell

Abstract

In Duchenne muscular dystrophy (DMD), dystrophin mutation leads to progressive lethal skeletal muscle degeneration. For unknown reasons, dystrophin deficiency does not recapitulate DMD in mice (mdx), which have mild skeletal muscle defects and potent regenerative capacity. We postulated that human DMD progression is a consequence of loss of functional muscle stem cells (MuSC), and the mild mouse mdx phenotype results from greater MuSC reserve fueled by longer telomeres. We report that mdx mice lacking the RNA component of telomerase (mdx/mTR) have shortened telomeres in muscle cells and severe muscular dystrophy that progressively worsens with age. Muscle wasting severity parallels a decline in MuSC regenerative capacity and is ameliorated histologically by transplantation of wild-type MuSC. These data show that DMD progression results, in part, from a cell-autonomous failure of MuSC to maintain the damage-repair cycle initiated by dystrophin deficiency. The essential role of MuSC function has therapeutic implications for DMD.

Authors+Show Affiliations

Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21145579

Citation

Sacco, Alessandra, et al. "Short Telomeres and Stem Cell Exhaustion Model Duchenne Muscular Dystrophy in mdx/mTR Mice." Cell, vol. 143, no. 7, 2010, pp. 1059-71.
Sacco A, Mourkioti F, Tran R, et al. Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell. 2010;143(7):1059-71.
Sacco, A., Mourkioti, F., Tran, R., Choi, J., Llewellyn, M., Kraft, P., Shkreli, M., Delp, S., Pomerantz, J. H., Artandi, S. E., & Blau, H. M. (2010). Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell, 143(7), 1059-71. https://doi.org/10.1016/j.cell.2010.11.039
Sacco A, et al. Short Telomeres and Stem Cell Exhaustion Model Duchenne Muscular Dystrophy in mdx/mTR Mice. Cell. 2010 Dec 23;143(7):1059-71. PubMed PMID: 21145579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. AU - Sacco,Alessandra, AU - Mourkioti,Foteini, AU - Tran,Rose, AU - Choi,Jinkuk, AU - Llewellyn,Michael, AU - Kraft,Peggy, AU - Shkreli,Marina, AU - Delp,Scott, AU - Pomerantz,Jason H, AU - Artandi,Steven E, AU - Blau,Helen M, Y1 - 2010/12/09/ PY - 2010/05/18/received PY - 2010/09/18/revised PY - 2010/11/02/accepted PY - 2010/12/15/entrez PY - 2010/12/15/pubmed PY - 2011/1/15/medline SP - 1059 EP - 71 JF - Cell JO - Cell VL - 143 IS - 7 N2 - In Duchenne muscular dystrophy (DMD), dystrophin mutation leads to progressive lethal skeletal muscle degeneration. For unknown reasons, dystrophin deficiency does not recapitulate DMD in mice (mdx), which have mild skeletal muscle defects and potent regenerative capacity. We postulated that human DMD progression is a consequence of loss of functional muscle stem cells (MuSC), and the mild mouse mdx phenotype results from greater MuSC reserve fueled by longer telomeres. We report that mdx mice lacking the RNA component of telomerase (mdx/mTR) have shortened telomeres in muscle cells and severe muscular dystrophy that progressively worsens with age. Muscle wasting severity parallels a decline in MuSC regenerative capacity and is ameliorated histologically by transplantation of wild-type MuSC. These data show that DMD progression results, in part, from a cell-autonomous failure of MuSC to maintain the damage-repair cycle initiated by dystrophin deficiency. The essential role of MuSC function has therapeutic implications for DMD. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/21145579/Short_telomeres_and_stem_cell_exhaustion_model_Duchenne_muscular_dystrophy_in_mdx/mTR_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(10)01361-9 DB - PRIME DP - Unbound Medicine ER -