Bone tissue and muscle dystrophin deficiency in mdx mice

Nakagaki, Wilson Romero; Camilli, José Ângelo

doi:10.1016/j.jbspin.2011.08.004

Cited by 11 publications

(5 citation statements)

References 55 publications

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“…This causes an absence of the protein in the muscle, even though some rare revertant myofibers may be present (Sicinski et al, 1989;Hoffman et al, 1990). While in humans DMD leads to an early loss of muscle functionality, dystrophin-null mice show very mild symptoms until old age (Chamberlain et al, 2007), probably due to the presence of utrophin, an autosomal homologue of dystrophin in these animals (Nakagaki and Camilli, 2012). Hence, to obtain a phenotypic model closer to human disease, utrophin/dystrophin double-knockout mice have been created, which show a more severe phenotype and many signs of human dystrophy (i.e., severe muscle weakness, reduced lifespan, cardiomyopathy, and growth retardation) (Durbeej and Campbell, 2002;Vainzof et al, 2008).…”

Section: Animal Modelsmentioning

confidence: 99%

Nanoparticle Delivery of Antisense Oligonucleotides and Their Application in the Exon Skipping Strategy for Duchenne Muscular Dystrophy

Falzarano

Passarelli

Ferlini

2014

Nucleic Acid Therapeutics

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Section: Animal Modelsmentioning

confidence: 99%

Nanoparticle Delivery of Antisense Oligonucleotides and Their Application in the Exon Skipping Strategy for Duchenne Muscular Dystrophy

Falzarano

Passarelli

Ferlini

2014

Nucleic Acid Therapeutics

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“…Patients suffering from this disorder are left immobilized and eventually are often deceased around the age of 20 [16]. Duchenne muscular dystrophy is also known to lead to secondary osteoporosis and increased fracture risk, at least in part due to the reduced mobility of DMD patients [16, 17]. By improving both muscle and bone function and strength, patient mobility could be prolonged and quality of life increased.…”

Section: Introductionmentioning

confidence: 99%

Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy

Puolakkainen

Kainulainen

et al. 2017

BMC Musculoskelet Disord

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BackgroundInhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD.MethodsThirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks.ResultsTreatment of mdx mice with ActRIIB-Fc resulted in significantly increased body and muscle weights in both sedentary and exercising mice. Femoral μCT analysis showed increased bone volume and trabecular number (BV/TV +80%, Tb.N +70%, P < 0.05) in both ActRIIB-Fc treated groups. Running also resulted in increased bone volume and trabecular number in PBS-treated mice. However, there was no significant difference in trabecular bone structure or volumetric bone mineral density between the ActRIIB-Fc and ActRIIB-Fc-R indicating that running did not further improve bone structure in ActRIIB-Fc-treated mice. ActRIIB-Fc increased bone mass also in vertebrae (BV/TV +20%, Tb.N +30%, P < 0.05) but the effects were more modest. The number of osteoclasts was decreased in histological analysis and the expression of several osteoblast marker genes was increased in ActRIIB-Fc treated mice suggesting decreased bone resorption and increased bone formation in these mice. Increased bone mass in femurs translated into enhanced bone strength in biomechanical testing as the maximum force and stiffness were significantly elevated in ActRIIB-Fc-treated mice.ConclusionsOur results indicate that treatment of mdx mice with the soluble ActRIIB-Fc results in a robust increase in bone mass, without any additive effect by voluntary running. Thus ActRIIB-Fc could be an attractive option in the treatment of musculoskeletal disorders.

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“…Several new animal lines seem to be better models of the cardiac than of the skeletal aspects of DMD: the Cmah-/-;-mdx mouse, which carries a human-like mutation in a gene involved in sialylation [28,56]; the mdx/mTR mouse [27,57] which has shorter telomeres than the mdx mouse, as in the human disease; and a new mdx rat model [58]. Different mouse lines have been compared for studies of bone defects [59] which the mdx mouse does not mimic well [60] although it has been used successfully to study pharmacological effects on bone [61]. Finally, the GRMD, the dog line that best models DMD still diverges from the human disease and does not always show a severe pathology and shortened life.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of mdx mouse muscles reveals a signature of early human Duchenne muscular dystrophy

Ralston

Gutierrez-Cruz

Kenea

et al. 2021

Preprint

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The mdx mouse (C57BL/10ScSn-DMDmdx/J) is the oldest model of Duchenne muscular dystrophy (DMD). However, the mdx mouse has a nearly normal lifespan and mild pathology while DMD remains a severe, fatal disease. New mouse models that are more severely affected have not replaced the mdx mouse in DMD research. Here we report RNA-seq analysis of 55 wild-type and mdx mouse muscles: the hindlimb flexor digitorum brevis (FDB), extensor digitorum longus (EDL) and soleus (SOL) muscles, from 2- and 5-month-old mice. We investigate features of the mdx pathology and compare them with human DMD data. The mdx mouse muscles show enrichment of pathways related not only to inflammation and the immune response, but also to metabolic, developmental and structural pathways. The FDB shows a slower pathology development than EDL and SOL, in agreement with ex vivo experiments showing a similar age dependence of microtubule-related production of reactive oxygen species. Furthermore, the three mdx muscles show changes in over 80 genes affected in pre-symptomatic DMD patients. The mild pathology of the mdx mouse thus best mimics the early stages of DMD. This study should be helpful to those using mdx or mdx-derived mouse models to improve or develop DMD treatments.

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Bone tissue and muscle dystrophin deficiency in mdx mice

Cited by 11 publications

References 55 publications

Nanoparticle Delivery of Antisense Oligonucleotides and Their Application in the Exon Skipping Strategy for Duchenne Muscular Dystrophy

Nanoparticle Delivery of Antisense Oligonucleotides and Their Application in the Exon Skipping Strategy for Duchenne Muscular Dystrophy

Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy

Transcriptomic analysis of mdx mouse muscles reveals a signature of early human Duchenne muscular dystrophy

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