Dataset Information

The continuum of hybrid IIX/IIB fibers in normal mouse muscles: MHC isoform proportions and spatial distribution within single fibers.

ABSTRACT: Although skeletal muscle fiber types are often defined as belonging to discrete categories, many muscles possess fibers with intermediate phenotypes. These hybrid fiber types can be identified by their expression of two or more myosin heavy chain (MHC) isoforms within the same single fiber. In mouse muscles, the most common hybrid fibers are those coexpressing the IIX and IIB MHC isoforms. In the present study, we focused on these IIX/IIB fibers from normal mouse muscles to determine the relative proportions of MHC isoforms at both the protein and mRNA levels and to examine the longitudinal distribution of isoforms within single fibers. We found that IIX/IIB hybrids represent ?25 and 50% of the fibers in the mouse tibialis anterior and brachioradialis, respectively. The relative proportion of the IIX and IIB isoforms in these fibers spans a continuum, from predominantly IIB-like hybrids to IIX-like hybrids. Quantitative assessment of mRNA levels using real-time PCR from single fibers indicated that IIB expression dominated over IIX expression in most fibers and that a general correlation existed between mRNA isoform levels and MHC protein content. However, the match between mRNA levels and protein content was not precise. Finally, we measured MHC isoform proportions in adjacent fiber segments and discovered that ?30% of hybrids possessed significant differences in isoform content along their length. In some instances, the muscle fiber type as defined by MHC content changed completely along the length of a fiber. This pattern of asymmetrical MHC isoform content along the length of single fibers suggests that the multiple myonuclei of a muscle fiber may express distinct myofibrillar isoforms in an uncoordinated fashion.

SUBMITTER: Zhang MY

PROVIDER: S-EPMC3007186 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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The continuum of hybrid IIX/IIB fibers in normal mouse muscles: MHC isoform proportions and spatial distribution within single fibers.

Zhang Min Yi MY Zhang Wei Jie WJ Medler Scott S

American journal of physiology. Regulatory, integrative and comparative physiology 20100922 6

Although skeletal muscle fiber types are often defined as belonging to discrete categories, many muscles possess fibers with intermediate phenotypes. These hybrid fiber types can be identified by their expression of two or more myosin heavy chain (MHC) isoforms within the same single fiber. In mouse muscles, the most common hybrid fibers are those coexpressing the IIX and IIB MHC isoforms. In the present study, we focused on these IIX/IIB fibers from normal mouse muscles to determine the relativ ...[more]

PMID: 20861278

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Project description:BackgroundSelective pressure from pathogens is thought to shape the allelic diversity of major histocompatibility complex (MHC) genes in vertebrates. In particular, both local adaptation to pathogens and gene flow are thought to explain a large part of the intraspecific variation observed in MHC allelic diversity. To date, however, evidence that adaptation to locally prevalent pathogens maintains MHC variation is limited to species with limited dispersal and, hence, reduced gene flow. On the one hand high gene flow can disrupt local adaptation in species with high dispersal rates, on the other hand such species are much more likely to experience spatial variation in pathogen pressure, suggesting that there may be intense pathogen mediated selection pressure operating across breeding sites in panmictic species. Such pathogen mediated selection pressure operating across breeding sites should therefore be sufficient to maintain high MHC diversity in high dispersing species in the absence of local adaptation mechanisms. We used the Greater Flamingo, Phoenicopterus roseus, a long-lived colonial bird showing a homogeneous genetic structure of neutral markers at the scale of the Mediterranean region, to test the prediction that higher MHC allelic diversity with no population structure should occur in large panmictic populations of long-distance dispersing birds than in other resident species.ResultsWe assessed the level of allelic diversity at the MHC Class IIB exon 2 from 116 individuals born in four different breeding colonies of Greater Flamingo in the Mediterranean region. We found one of the highest allelic diversity (109 alleles, 2 loci) of any non-passerine avian species investigated so far relative to the number of individuals and loci genotyped. There was no evidence of population structure between the four major Mediterranean breeding colonies.ConclusionOur results suggest that local adaptation at MHC Class IIB in Greater Flamingos is constrained by high gene flow and high MHC diversity appears to be maintained by population wide pathogen-mediated selection rather than local pathogen-mediated selection. Further understanding of how pathogens vary across space and time will be crucial to further elucidate the mechanisms maintaining MHC diversity in species with large panmictic populations and high dispersal rates.

Project description:Skeletal muscles have a highly organized hierarchical structure, whose main function is to generate forces for movement and stability. To understand the complex heterogeneous behaviors of muscles, computational modeling has advanced as a non-invasive approach to evaluate relevant mechanical quantities. Aiming to improve musculoskeletal predictions, this paper presents a framework for modeling 3D deformable muscles that includes continuum constitutive representation, parametric determination, model validation, fiber distribution estimation, and integration of multiple muscles into a system level for joint motion simulation. The passive and active muscle properties were modeled based on the strain energy approach with Hill-type hyperelastic constitutive laws. A parametric study was conducted to validate the model using experimental datasets of passive and active rabbit leg muscles. The active muscle model with calibrated material parameters was then implemented to simulate knee bending during a squat with multiple quadriceps muscles. A computational fluid dynamics (CFD) fiber simulation approach was utilized to estimate the fiber arrangements for each muscle, and a cohesive contact approach was applied to simulate the interactions among muscles. The single muscle simulation results showed that both passive and active muscle elongation responses matched the range of the testing data. The dynamic simulation of knee flexion and extension showed the predictive capability of the model for estimating the active quadriceps responses, which indicates that the presented modeling pipeline is effective and stable for simulating multiple muscle configurations. This work provided an effective framework of a 3D continuum muscle model for complex muscle behavior simulation, which will facilitate additional computational and experimental studies of skeletal muscle mechanics. This study will offer valuable insight into the future development of multiscale neuromuscular models and applications of these models to a wide variety of relevant areas such as biomechanics and clinical research.

Dataset Information

The continuum of hybrid IIX/IIB fibers in normal mouse muscles: MHC isoform proportions and spatial distribution within single fibers.

Publications

The continuum of hybrid IIX/IIB fibers in normal mouse muscles: MHC isoform proportions and spatial distribution within single fibers.

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