Molecular, cellular and physiological investigation of myostatin propeptide-mediated muscle growth in adult mice

Tissue-resident macrophages can originate from embryonic or adult hematopoiesis. They play important roles in a wide range of biological processes including tissue remodeling during organogenesis, organ homeostasis, repair following injury, and immune response to pathogens. Although the origins and tissue-specific functions of resident macrophages have been extensively studied in many other tissues, they are not well characterized in skeletal muscle. In the present study, we have characterized the ontogeny of skeletal muscle-resident macrophages by lineage tracing and bone marrow transplant experiments. We demonstrate that skeletal muscle-resident macrophages originate from both embryonic hematopoietic progenitors located within the yolk sac and fetal liver as well as definitive hematopoietic stem cells located within the bone marrow of adult mice. Single-cell-based transcriptome analyses revealed that skeletal muscle-resident macrophages are distinctive from resident macrophages in other tissues as they express a distinct complement of transcription factors and are composed of functionally diverse subsets correlating to their origins. Functionally, skeletal muscle-resident macrophages appear to maintain tissue homeostasis and promote muscle growth and regeneration.

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Relation between extent of myostatin depletion and muscle growth in mature mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00179.2009 ◽

2009 ◽

Vol 297 (4) ◽

pp. E935-E940 ◽

Cited By ~ 23

Author(s):

Stephen Welle ◽

Kerri Burgess ◽

Charles A. Thornton ◽

Rabi Tawil

Keyword(s):

Muscle Mass ◽

Normal Level ◽

Muscle Growth ◽

Mapk Signaling ◽

Negative Regulator ◽

Adult Mice ◽

Fiber Size ◽

Myonuclear Domain ◽

Potential Strategy ◽

Mapk Signaling Pathways

Myostatin is a negative regulator of muscle growth and fiber size. Changes in myostatin expression might contribute to changes in muscle mass associated with various conditions, and reducing the amount of active myostatin is a potential strategy for preventing or reversing muscle atrophy. The present study was done to determine the extent to which myostatin levels must decline to induce growth of mature muscles. Myostatin expression was reduced by activating Cre recombinase in adult mice with floxed myostatin genes. The duration of Cre activation varied from 1 to 6 wk, and the residual myostatin mRNA expression after Cre activation varied from 3 to 63% of the normal level. Promyostatin levels declined in parallel with myostatin mRNA. There was no increase in muscle mass over the 3 mo following Cre activation if residual myostatin expression was ≥40% of normal. In mice with <40% of normal myostatin expression, muscle mass increased in proportion to the extent of myostatin depletion. In mice with ≤10% of normal myostatin expression, muscle mass increased ∼25%. Myostatin depletion increased myonuclear domain volumes and the ratio of RNA to myonuclei probably by enhancing DNA transcription rather than by inhibiting RNA decay. There was no evidence that maintenance of the hypertrophy during chronic myostatin deficiency requires altered activity of Akt/mTOR or p38 MAPK signaling pathways. These data suggest that anabolic therapies based on reducing the concentration of active myostatin will be effective only if a very large proportion of the myostatin is removed or inactivated.

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Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00268.2004 ◽

2005 ◽

Vol 288 (1) ◽

pp. E92-E105 ◽

Cited By ~ 69

Author(s):

Anthony D. Gagliardi ◽

Evan Y. W. Kuo ◽

Sanda Raulic ◽

Graham F. Wagner ◽

Gabriel E. DiMattia

Keyword(s):

Skeletal Muscle ◽

Transgenic Mice ◽

Growth Retardation ◽

Bone Development ◽

Muscle Growth ◽

Growth Inhibitor ◽

Neonatal Morbidity ◽

Postnatal Growth ◽

Adult Mice ◽

Potent Growth

Stanniocalcin (STC)-2 was discovered by its primary amino acid sequence identity to the hormone STC-1. The function of STC-2 has not been examined; thus we generated two lines of transgenic mice overexpressing human (h)STC-2 to gain insight into its potential functions through identification of overt phenotypes. Analysis of mouse Stc2 gene expression indicates that, unlike Stc1, it is not highly expressed during development but exhibits overlapping expression with Stc1 in adult mice, with heart and skeletal muscle exhibiting highest steady-state levels of Stc2 mRNA. Constitutive overexpression of hSTC-2 resulted in pre- and postnatal growth restriction as early as embryonic day 12.5, progressing such that mature hSTC-2-transgenic mice are ∼45% smaller than wild-type littermates. hSTC-2 overexpression is sometimes lethal; we observed 26–34% neonatal morbidity without obvious dysmorphology. hSTC-2-induced growth retardation is associated with developmental delay, most notably cranial suture formation. Organ allometry studies show that hSTC-2-induced dwarfism is associated with testicular organomegaly and a significant reduction in skeletal muscle mass likely contributing to the dwarf phenotype. hSTC-2-transgenic mice are also hyperphagic, but this does not result in obesity. Serum Ca2+ and PO4 were unchanged in hSTC-2-transgenic mice, although STC-1 can regulate intra- and extracellular Ca2+ in mammals. Interestingly, severe growth retardation induced by hSTC-2 is not associated with a decrease in GH or IGF expression. Consequently, similar to STC-1, STC-2 can act as a potent growth inhibitor and reduce intramembranous and endochondral bone development and skeletal muscle growth, implying that these tissues are specific physiological targets of stanniocalcins.

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Glycine receptor subunit-ß -deficiency in a mouse model of spasticity results in attenuated physical performance, growth and muscle strength

10.1101/2020.07.15.180976 ◽

2020 ◽

Author(s):

Cintia Rivares ◽

Alban Vignaud ◽

Wendy Noort ◽

Bastijn Koopmans ◽

Maarten Loos ◽

...

Keyword(s):

Physical Activity ◽

Skeletal Muscle ◽

Physical Performance ◽

Motor Function ◽

Glycine Receptor ◽

Muscle Fibers ◽

Muscle Growth ◽

Skeletal Muscle Function ◽

Cross Sectional ◽

Adult Mice

AbstractSpasticity is the most common neurological disorder associated with increased muscle contraction causing impaired movement and gait. The aim of this study was to characterize physical performance and skeletal muscle function and phenotype of mice with a hereditary spastic mutation (B6.Cg-Glrbspa/J). Motor function, gait and physical activity of juvenile and adult spastic mice and the morphological, histological and mechanical characteristics of their soleus (SO) and gastrocnemius medialis (GM) muscles were compared with their wild-type (WT) littermates. Spastic mice showed attenuated growth, impaired motor function and low physical activity. Gait of spastic mice was characterized by a typical hopping pattern. Spastic mice showed lower muscle forces, which were related to the smaller physiological cross-sectional area of spastic muscles. The muscle-tendon complex length-force relationship of adult GM was shifted towards shorter lengths, which was explained by attenuated longitudinal tibia growth. Spastic GM was more fatigue resistant than WT GM. This was largely explained by a higher mitochondrial content in muscle fibers and relatively higher percentage of slow type muscle fibers. Muscles of juvenile spastic mice showed similar differences compared to WT juvenile mice, but these were less pronounced than between adult mice. This study shows that in spastic mice, disturbed motor function and gait is likely the result hyperactivity of skeletal muscle and impaired skeletal muscle growth, which progress with age.

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Binucleate Spermiogenesis in the Mouse

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010009381x ◽

1972 ◽

Vol 30 ◽

pp. 112-113

Author(s):

John J. Wolosewick

Keyword(s):

Electron Microscopy ◽

Phosphate Buffer ◽

Seminiferous Epithelium ◽

Mouse Testis ◽

Germinal Epithelium ◽

Intercellular Bridges ◽

Adult Mice ◽

Cervical Dislocation ◽

Human And Mouse

Classically, the male germinal epithelium is depicted as synchronously developing uninucleate spermatids conjoined by intercellular bridges. Recently, binucleate and multinucleate spermatids from human and mouse testis have been reported. The present paper describes certain developmental events in one type of binucleate spermatid in the seminiferous epithelium of the mouse.Testes of adult mice (ABP Jax) were removed from the animals after cervical dislocation and placed into 2.5% glutaraldehyde/Millonig's phosphate buffer (pH 7.2). Testicular capsules were gently split and separated, exposing the tubules. After 15 minutes the tissue was carefully cut into cubes (approx. 1mm), fixed for an additional 45 minutes and processed for electron microscopy.

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Ineffective Thrombopoiesis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158881 ◽

1990 ◽

Vol 48 (3) ◽

pp. 266-267

Author(s):

JM Radley ◽

SL Ellis

Keyword(s):

Microscopic Examination ◽

Phosphate Buffer ◽

Primary Myelofibrosis ◽

Transient Increase ◽

Major Difficulty ◽

Adult Mice ◽

Dense Cytoplasm

In effective thrombopoies is has been inferred to occur in several disease sates from considerations of megakaryocyte mass and platelet kinetics. Microscopic examination has demonstrated increased numbers of megakaryocytes, with a typical forms particularly pronounced, in primary myelofibrosis. It has not been documented if megakaryocyte ever fail to reach maturity in non-pathological situations. A major difficulty of establishing this is that the number of megakaryocytes normally present in the marrow is extremely low. A large transient increase in megakaryocytopoiesis can how ever be induced in mice by an injection of 5-fluorouracil. We have utilised this treatment and report here evidence for in effective thrombopoies is in healthy mice.Adult mice were perfused (2% glutaraldehyde in 0.08M phosphate buffer, pH 7.4) 8 days following an injection of 5-fluorouracil (150mg/kg). Femurs were subsequently decalcified in 10% neutral E.D.T.A. and embedded in Spurrs resin. Transverse sections of marrow revealed many megakaryocytes at various stages of maturity. Occasional megakaryocytes (less than 1%) were found to be under going degeneration prior to achieving full maturation and releasing cytoplasm as platelets. These cells were characterized by a peripheral rim of dense cytoplasm which enveloped a mass of organelles and vacuoles (Fig. 1). Numerous microtubules were foundaround and with in the organelle-rich zone (Fig 2).

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