P.265Integrating clinical outcome measures, MRI and circulating biomarkers in subjects with Becker muscular dystrophy: a prospective longitudinal study
Zaïda KoeksN. van de VeldeNicolaas A. VerweyValeria RicottiKristy J. BrownGautam SajeevJ. SignorovitchPietro SpitaliHermien E. KanE. Niks
0
Citation
0
Reference
10
Related Paper
Keywords:
Muscle weakness
Nonsense mutation
mdx mouse
Cite
Citations (4)
mdx mouse
Utrophin
Cite
Citations (135)
Exon skipping
Cite
Citations (142)
Dystrophin, surmised to be the causative protein of Duchenne muscular dystrophy (DMD), was studied for its intracellular localization and characterization by immunostaining and Western blotting using antidystrophin antibodies. In normal controls and in patients with various neuromuscular diseases other than DMD and Becker's muscular dystrophy (BMD), dystrophin was detected homogeneously on the entire surface membrane of the muscle fibers, whereas it was absent in DMD patients and partially observed in BMD cases. The density of dystrophin was low in BMD and female DMD patients. In mouse skeletal and cardiac muscles, too, dystrophin localized in the muscle surface membrane, and its presence in the brain was also suggested. However, dystrophin was not detected in mdx mice. These data suggest that myofiber necrosis in DMD patients and mdx mice is likely to be the result of plasma membrane instability.
Immunostaining
mdx mouse
ITGA7
Cite
Citations (33)
ITGA7
Cite
Citations (429)
Duchenne muscular dystrophy (DMD) affects besides muscle also the brain, resulting in memory and behavioral problems. The consequences of dystrophinopathy on gross macroscopic alterations are unclear. To elucidate the effect of full-length dystrophin expression on brain morphology, we used high-resolution post-mortem MRI in mouse models that either express 0% (mdx), 100% (BL10) or a low amount of full-length dystrophin (mdx-XistΔhs). While absence or low amounts of full-length dystrophin did not significantly affect whole brain volume and skull morphology, we found differences in volume of individual brain structures. The results are in line with observations in humans, where whole brain volume was found to be reduced only in patients lacking both full-length dystrophin and the shorter isoform Dp140.
Utrophin
mdx mouse
Cite
Citations (12)
Immunofluorescence
Cite
Citations (5)
mdx mouse
Exosome
Dilated Cardiomyopathy
Cite
Citations (20)
Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration.Mutations in the DMD gene result in the absence of dystrophin, a protein required for muscle strength and stability.Currently, there is no cure for DMD.Since murine models are relatively easy to genetically manipulate, cost effective, and easily reproducible due to their short generation time, they have helped to elucidate the pathobiology of dystrophin deficiency and to assess therapies for treating DMD.Recently, several murine models have been developed by our group and others to be more representative of the human DMD mutation types and phenotypes.For instance, mdx mice on a DBA/2 genetic background, developed by Fukada et al., have lower regenerative capacity and exhibit very severe phenotype.Cmah-deficient mdx mice display an accelerated disease onset and severe cardiac phenotype due to differences in glycosylation between humans and mice.Other novel murine models include mdx52, which harbors a deletion mutation in exon 52, a hot spot region in humans, and dystrophin/utrophin double-deficient (dko), which displays a severe dystrophic phenotype due the absence of utrophin, a dystrophin homolog.This paper reviews the pathological manifestations and recent therapeutic developments in murine models of DMD such as standard mdx (C57BL/10), mdx on C57BL/6 background (C57BL/6-mdx), mdx52, dystrophin/utrophin double-deficient (dko), mdx geo , Dmd-null, humanized DMD (hDMD), mdx on DBA/2 background (DBA/2-mdx), Cmah-mdx, and mdx/mTRKO murine models.
Utrophin
mdx mouse
Exon skipping
Cite
Citations (46)