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Journal of Cell Biology (JCB) publishes advances in any area of basic cell biology as well as applied cellular advances in fields such as immunology, neurobiology, metabolism, microbiology, developmental biology, and plant biology. Est. 1955
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Journal of Experimental Medicine (JEM) publishes papers providing novel conceptual insight into immunology, neuroscience, cancer biology, vascular biology, microbial pathogenesis, and stem cell biology. Est. 1896
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Journal of General Physiology (JGP) publishes mechanistic and quantitative cellular and molecular physiology of the highest quality. Est. 1918
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Body weight and phenotypic characteristics of Ho mice. (A)  Body weight cur...
Published: 04 March 2024
Figure 1. Body weight and phenotypic characteristics of Ho mice. (A) Body weight curves of WT (black squares) and Ho (red circles) over a period of 17 wk. Each symbol represents the body weight mean (±SD) of 9–12 mice. Statistical analysis was performed using two-way ANOVA, followed by the Bonferroni post-hoc test (*P < 0.05). (B) Genotype frequency of heterozygous × heterozygous breeding cages. Total n males = 593, total n females = 480. These frequencies are significantly different than the expected genotype frequencies for the χ2 test, with a two-tailed P value of 1.154572E-4 and 6.879268E-7, respectively. (C) Photograph of gravid uteri (left) and fetuses (right) harvested from Ho females bred with heterozygous males. Fetuses were harvested at 14.5 dpc and genotyped. No difference in size or appearance is noticeable between genotypes. More about this image found in Body weight and phenotypic characteristics of Ho mice. (A) Body weight cur...
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In vivo muscle function is negatively affected by the presence of the Ho p....
Published: 04 March 2024
Figure 2. In vivo muscle function is negatively affected by the presence of the Ho p.F4976L Ryr1 mutation. (A) Voluntary running distance and speed of WT (n = 13) and Ho (n = 14) mice (starting age = 10–13 wk) measured for a period of 22 days. Data points are expressed as mean ± SEM. Left panel shows the spontaneous locomotor cumulative distance (km) recorded during the dark phase period (5 pm–5 am). Right panel shows the average running speed (km/hour) recorded during the night phase (5 pm–5 am). Statistical analysis was performed using ANOVA, followed by the Bonferroni post hoc test. *P < 0.05. (B) Analysis of forelimb (anterior two paws) grip strength in WT (n = 15) and Ho (n = 15) littermates. Mice were tested once per week for a period of 12 wk starting from 6 wk of age. Five measurements for each mouse were averaged. Each point represents the mean ± SEM. ANOVA, followed by the Bonferroni post hoc test. *P < 0.05. (C) Comparison between the distance run by WT and Ho mice during the exhaustion treadmill test. The distance run by Ho is 36% shorter than the one run by WT littermates. Each point represents the measurement coming from a single mouse. Bars represent mean ± SD. Homozygous mice run significantly less than WT. Statistical analysis was performed using ANOVA, followed by the Bonferroni post-hoc test. ***P < 0.001. More about this image found in In vivo muscle function is negatively affected by the presence of the Ho p....
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The mechanical properties of muscles are impacted by the presence of the ho...
Published: 04 March 2024
Figure 3. The mechanical properties of muscles are impacted by the presence of the homozygous p.F4976L mutation. (A) Representative traces and force plots of EDL muscles during either twitch (upper panels) or tetanic (lower panels) stimulation. (B) Representative traces and force plots of sole... More about this image found in The mechanical properties of muscles are impacted by the presence of the ho...
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EDL and soleus from homozygous mice do not show any sign of fiber type swit...
Published: 04 March 2024
Figure 4. EDL and soleus from homozygous mice do not show any sign of fiber type switch or atrophy. (A and C) Representative images of EDL and soleus muscle sections from WT and Ho littermates, scale bars 500 μm (upper panels) and 200 μm (lower panels). Muscle sections were stained with specific... More about this image found in EDL and soleus from homozygous mice do not show any sign of fiber type swit...
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Electrically evoked calcium transients and resting [Ca <sup> 2+ </sup> ] in...
Published: 04 March 2024
Figure 5. Electrically evoked calcium transients and resting [Ca 2+ ] in FDB fibers and single channel recordings. (A) Representative traces of MagFluo-4 fluorescence changes in single FDB fibers from WT (n = 4 mice) and Ho (n = 6 mice) after twitch and tetanic stimulation (top and lower panels, respectively). Statistical analysis was performed using the Mann–Whitney test (*P < 0.05; ***P < 0.001). Each symbol represents the value from a single fiber. (B) Analysis of the resting [Ca2+] levels (Fura-2 fluorescent ratio) in FDB fibers from WT (n = 4 mice) and Ho littermates (n = 3 mice) (ANOVA, followed by the Bonferroni post-hoc test **P < 0.001). (C) Representative trace and bar plots of total calcium store release after the application 10 µM ionomycin + 30 µM CPA and 100 µM La3+ to FDB fibers. Right panel: Each symbol represents the mean value from 2–4 fibers from a single mouse. Bars show means and error bars show SEM. Statistical analysis was performed using Mann–Whitney test (**P < 0.001). (D) Left panel: Representative single-channel RyR1 current fluctuations from WT (lefthand panels) and Ho (righthand panels) mice in the presence of 3 µM Ca2+ (top traces), 100 µM Ca2+ (middle traces), and 1 mM Ca2+ (bottom traces**). O and C indicate the open and closed channel levels, respectively. The Po value above each trace refers to the average Po determined over a 3-min period for that channel. Right panel: Bar plot of Po of WT and Ho channels when at different concentrations of Ca2+. Ho channels show higher opening probabilities at 20 µM, 100 µM, and 1 mM calcium. More about this image found in Electrically evoked calcium transients and resting [Ca 2+ ] in...
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Biochemical analysis of EDL, soleus, and EOM muscles. (A and B)  Western bl...
Published: 04 March 2024
Figure 6. Biochemical analysis of EDL, soleus, and EOM muscles. (A and B) Western blot analysis of the major excitation–contraction proteins in EDL and soleus muscles from WT and Ho adult mice (Mann–Whitney test; *P < 0.05). The representative immunopositive bands are shown on the left of eac... More about this image found in Biochemical analysis of EDL, soleus, and EOM muscles. (A and B) Western bl...
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Electron microscopy (EM) analysis of EDL and soleus muscles from WT and Ho ...
Published: 04 March 2024
Figure 7. Electron microscopy (EM) analysis of EDL and soleus muscles from WT and Ho mice. (A) Panels a, b, d, and e show representative longitudinal (a and b) and transversal (d and e) EM images at low-medium magnifications of EDL fibers from WT (a and d) and Ho (b and e) mice. In a the typical... More about this image found in Electron microscopy (EM) analysis of EDL and soleus muscles from WT and Ho ...
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Position of the p.F4976L mutation in the RyR1 structure.  (A)  The left pan...
Published: 04 March 2024
Figure 8. Position of the p.F4976L mutation in the RyR1 structure. (A) The left panel shows a schematic representation of a longitudinal section of the RyR1 and its subdomains. The F4976L mutation (corresponding F4975L in the rabbit structure) is present within the CTD domain (dark red). The right panel shows a zoomed-in view of the region surrounding the mutation (shown in cyan). The right panel also shows the location of a neighboring ATP binding domain (green), Zn2+-binding domain (violet), Ca2+-binding domain (yellow), and caffeine-binding domain (magenta). (B) The F4976L (F4975 in the rabbit structure) mutation is close to the ATP binding site. The substitution of the phenylalanine (F) residue with a leucine (L) residue does not affect the overall charges, but could rather cause a steric modification. The leucine residue could participate in possible clashes with the neighboring F4968 and S4965. The analyzed structure has the PDB ID code 5TAL . More about this image found in Position of the p.F4976L mutation in the RyR1 structure. (A) The left pan...
Journal Articles