2016
DOI: 10.1093/hmg/ddw111
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Klotho gene silencing promotes pathology in themdxmouse model of Duchenne muscular dystrophy

Abstract: Duchenne muscular dystrophy (DMD) is a lethal muscle disease involving progressive loss of muscle regenerative capacity and increased fibrosis. We tested whether epigenetic silencing of the klotho gene occurs in the mdx mouse model of DMD and whether klotho silencing is an important feature of the disease. Our findings show that klotho undergoes muscle-specific silencing at the acute onset of mdx pathology. Klotho experiences increased methylation of CpG sites in its promoter region, which is associated with g… Show more

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Cited by 41 publications
(90 citation statements)
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“…Currently, there is no effective therapy for DMD and transplanting muscle stem cells into damaged organs to stop disease progression has proven difficult (Sienkiewicz et al, 2015). Recent studies have demonstrated that klotho is epigenetically silenced in muscle cells of mdx mice at the time of disease onset, and systemic expression of klotho via a transgene can relieve disease symptoms (Wehling-Henricks et al, 2016). Therefore, we injected AAV-dgKlotho-MPH into neonatal Cas9/mdx mutant mice via facial vein injection.…”
Section: Resultsmentioning
confidence: 99%
“…Currently, there is no effective therapy for DMD and transplanting muscle stem cells into damaged organs to stop disease progression has proven difficult (Sienkiewicz et al, 2015). Recent studies have demonstrated that klotho is epigenetically silenced in muscle cells of mdx mice at the time of disease onset, and systemic expression of klotho via a transgene can relieve disease symptoms (Wehling-Henricks et al, 2016). Therefore, we injected AAV-dgKlotho-MPH into neonatal Cas9/mdx mutant mice via facial vein injection.…”
Section: Resultsmentioning
confidence: 99%
“…Of note, the full-length α-klotho protein was not found in any skeletal muscle; 65-kDa and 95-kDa α-klotho proteins were found in the Qua, Gas, and TA, but the expression of the 65-kDa α-klotho protein was low in the TA. In contrast, Wehling-Henricks et al (2016) showed that the full-length α-klotho protein was expressed in the skeletal muscle using Western blot (ab75023, Abcam). The conflicting results are most likely due to the difference in the antibodies used.…”
Section: Discussionmentioning
confidence: 99%
“…Primary myoblasts were isolated following a previous protocol (Wehling‐Henricks et al, 2016) and detailed in Supporting Information Appendix S1 and then cultured on coverslips. After 6 days of growth in differentiation medium to induce cell fusion, cells on the coverslips were immunolabeled with rabbit antidesmin.…”
Section: Methodsmentioning
confidence: 99%