Biomedical Engineering Reference
In-Depth Information
Prednisone
EGGG
Dantrolene
140
120
100
80
60
40
20
0
140.0
120.0
100.0
80.0
60.0
40.0
20.0
0.0
140
120
100
80
60
40
20
0
0
50
100
150
0
50
100
150
0
50
100
150
Concentration (μM)
Concentration (μM)
Concentration (μM)
MG132
TSA
140
300
250
200
150
100
50
0
120
100
80
60
40
20
0
0
0.1
0.2
0.3
0.4
0
10
20
30
40
Concentration (μM)
Concentration (μM)
Figure 18.9
Dose-response curves for drug effects on ROS level of MD zebrafish. Three dpf
animals were stained with H
2
DCFDA and processed for morphometric analysis. Each point represents
meanSE (
n
¼8-10).
18.3.12 Confirmation of Prednisone Effects on
Muscle Structure by Histology
Since prednisone treatment decreased MD effects on myotome length and ROS level,
we next examined effects on muscle structure using histology. As observed in
previous experiments, untreated MD zebrafish exhibited MD muscle phenotypes,
including small muscle fibers, loss of V-shaped myotomes, centralized nuclei, and
disorganized muscle fibers. In contrast, muscle structure in prednisone-treated 3dpf
MD zebrafish resembled 3dpf KD control zebrafish, including large muscle fibers,
less centralized nuclei, and straight muscle fibers with clear midline; V-shaped
myotomes were still absent. These results indicated that prednisone treatment
partially inhibited progression of MD phenotypes (data not shown).
18.4 DISCUSSION
Although several different mouse MD models have been developed, a consistent
phenotype has not yet been generated, contributing to the difficulty of using
mammalianmodels for drug screening. In contrast tomurine dystroglycan knockouts,
dystroglycan KD zebrafish can survive up to 10dpf, indicating that dystroglycan is
dispensable for basement membrane formation during early development. However,
disruption of DGC in dystroglycan KD zebrafish leads to loss of sarcomere and
sarcoplasmic organization, indicating that dystroglycan is required to maintain long-
term muscle cell survival in zebrafish.
Search WWH ::
Custom Search