Usage Information
Citation Information: JCI Insight. 2022;7(15):e157336. https://doi.org/10.1172/jci.insight.157336.
Abstract
Striated preferentially expressed protein kinase (SPEG), a myosin light chain kinase, is mutated in centronuclear myopathy (CNM) and/or dilated cardiomyopathy. No precise therapies are available for this disorder, and gene replacement therapy is not a feasible option due to the large size of SPEG. We evaluated the potential of dynamin-2 (DNM2) reduction as a potential therapeutic strategy because it has been shown to revert muscle phenotypes in mouse models of CNM caused by MTM1, DNM2, and BIN1 mutations. We determined that SPEG-β interacted with DNM2, and SPEG deficiency caused an increase in DNM2 levels. The DNM2 reduction strategy in Speg-KO mice was associated with an increase in life span, body weight, and motor performance. Additionally, it normalized the distribution of triadic proteins, triad ultrastructure, and triad number and restored phosphatidylinositol-3-phosphate levels in SPEG-deficient skeletal muscles. Although DNM2 reduction rescued the myopathy phenotype, it did not improve cardiac dysfunction, indicating a differential tissue-specific function. Combining DNM2 reduction with other strategies may be needed to target both the cardiac and skeletal defects associated with SPEG deficiency. DNM2 reduction should be explored as a therapeutic strategy against other genetic myopathies (and dystrophies) associated with a high level of DNM2.
Authors
Qifei Li, Jasmine Lin, Jeffrey J. Widrick, Shiyu Luo, Gu Li, Yuanfan Zhang, Jocelyn Laporte, Mark A. Perrella, Xiaoli Liu, Pankaj B. Agrawal
Usage data is cumulative from June 2022 through April 2023.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 4,716 | 77 |
| 560 | 11 | |
| Figure | 356 | 0 |
| Table | 34 | 0 |
| Supplemental data | 192 | 7 |
| Citation downloads | 66 | 0 |
| Totals | 5,924 | 95 |
| Total Views | 6,019 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
