Single Cell ADNP Predictive of Human Muscle Disorders: Mouse Knockdown Results in Muscle Wasting
| العنوان: | Single Cell ADNP Predictive of Human Muscle Disorders: Mouse Knockdown Results in Muscle Wasting |
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| المؤلفون: | Gidon Karmon, Eliezer Giladi, Lior Bikovski, Adva Hadar, Iman Jaljuli, Illana Gozes, Shlomo Sragovich, Tal Iram, Róbert Pálovics, Oxana Kapitansky, Meishar Shahoha |
| المصدر: | Cells, Vol 9, Iss 2320, p 2320 (2020) Cells Volume 9 Issue 10 |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Male, muscular dystrophy, Myosin light-chain kinase, Neuromuscular Junction, Nerve Tissue Proteins, neuromuscular diseases, Biology, Motor Activity, Neuroprotection, Article, Transcriptome, Mice, Muscular Diseases, Physical Conditioning, Animal, medicine, Animals, Humans, Microtubule end, RNA, Messenger, Muscular dystrophy, Myopathy, Child, Gait, CRISPR/Cas9, lcsh:QH301-705.5, ADNP, Homeodomain Proteins, Mice, Knockout, Gene knockdown, Base Sequence, Behavior, Animal, Wasting Syndrome, Muscles, Stem Cells, General Medicine, medicine.disease, Cell biology, NAP, MYL2, Gene Expression Regulation, lcsh:Biology (General), Gene Knockdown Techniques, NIH 3T3 Cells, Female, medicine.symptom, Single-Cell Analysis, Naphthoquinones, RNA, Guide, Kinetoplastida |
| الوصف: | Activity-dependent neuroprotective protein (ADNP) mutations are linked with cognitive dysfunctions characterizing the autistic-like ADNP syndrome patients, who also suffer from delayed motor maturation. We thus hypothesized that ADNP is deregulated in versatile myopathies and that local ADNP muscle deficiency results in myopathy, treatable by the ADNP fragment NAP. Here, single-cell transcriptomics identified ADNP as a major constituent of the developing human muscle. ADNP transcript concentrations further predicted multiple human muscle diseases, with concentrations negatively correlated with the ADNP target interacting protein, microtubule end protein 1 (EB1). Reverting back to modeling at the single-cell level of the male mouse transcriptome, Adnp mRNA concentrations age-dependently correlated with motor disease as well as with sexual maturation gene transcripts, while Adnp expressing limb muscle cells significantly decreased with aging. Mouse Adnp heterozygous deficiency exhibited muscle microtubule reduction and myosin light chain (Myl2) deregulation coupled with motor dysfunction. CRISPR knockdown of adult gastrocnemius muscle Adnp in a Cas9 mouse resulted in treadmill (male) and gait (female) dysfunctions that were specifically ameliorated by treatment with the ADNP snippet, microtubule interacting, Myl2&mdash regulating, NAP (CP201). Taken together, our studies provide new hope for personalized diagnosis/therapeutics in versatile myopathies. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a0a85f0fed5d1aa5596301ea39d9b247Test https://www.mdpi.com/2073-4409/9/10/2320Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a0a85f0fed5d1aa5596301ea39d9b247 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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