Gene expression profiling of gastrocnemius of “minimuscle” mice

Burniston, Jatin G.; Meek, Thomas H.; Pandey, Sachchida Nand; Broitman-Maduro, Gina; Maduro, Morris; Bronikowski, Anne M.; Garland, Theodore; Chen, Yiwen

doi:10.1152/physiolgenomics.00149.2012

Cited by 10 publications

(8 citation statements)

References 47 publications

(56 reference statements)

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“…Albumin is a prominent feature of the skeletal muscle proteome [22] but expression of the albumin gene is low in muscle [23]. Therefore, our findings support the conclusion that albumin extracted from muscle is primarily synthesised in the liver, which typically has a more rapid turnover of proteins than striated muscle [24].…”

Section: Discussionsupporting

confidence: 81%

“…The modification to albumin may occur directly within the liver or secondarily in the periphery where the shift toward a more acidic isoelectric point might be associated with lesser uptake/residency in the muscle interstitium. Alternatively, because albumin mRNA can be detected (albeit at low levels) in skeletal muscle [23] the relatively acidic species of albumin {ALBU (ii)} might represent protein that was synthesised and modified in the muscle rather than the liver. In the future, inclusion of hepatic tissue alongside the collection of various striated muscles from endurance-trained or chronically stimulated animals might resolve some of these unanswered questions.…”

Section: Discussionmentioning

confidence: 99%

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On the Rate of Synthesis of Individual Proteins within and between Different Striated Muscles of the Rat

et al. 2016

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The turnover of muscle protein is responsive to different (patho)-physiological conditions but little is known about the rate of synthesis at the level of individual proteins or whether this varies between different muscles. We investigated the synthesis rate of eight proteins (actin, albumin, ATP synthase alpha, beta enolase, creatine kinase, myosin essential light chain, myosin regulatory light chain and tropomyosin) in the extensor digitorum longus, diaphragm, heart and soleus of male Wistar rats (352 ± 30 g body weight). Animals were assigned to four groups (n = 3, in each), including a control and groups that received deuterium oxide (2H2O) for 4 days, 7 days or 14 days. Deuterium labelling was initiated by an intraperitoneal injection of 10 μL/g body weight of 99.9% 2H2O-saline, and was maintained by administration of 5% (v/v) 2H2O in drinking water provided ad libitum. Homogenates of the isolated muscles were analysed by 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionisation time of flight mass spectrometry. Proteins were identified against the SwissProt database using peptide mass fingerprinting. For each of the eight proteins investigated, the molar percent enrichment (MPE) of 2H and rate constant (k) of protein synthesis was calculated from the mass isotopomer distribution of peptides based on the amino acid sequence and predicted number of exchangeable C–H bonds. The average MPE (2.14% ± 0.2%) was as expected and was consistent across muscles harvested at different times (i.e., steady state enrichment was achieved). The synthesis rate of individual proteins differed markedly within each muscle and the rank-order of synthesis rates differed among the muscles studied. After 14 days the fraction of albumin synthesised (23% ± 5%) was significantly (p < 0.05) greater than for other muscle proteins. These data represent the first attempt to study the synthesis rates of individual proteins across a number of different striated muscles.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

On the Rate of Synthesis of Individual Proteins within and between Different Striated Muscles of the Rat

et al. 2016

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“…Differential expression analysis revealed that, consistent with the known reduction of type IIB fibers (Guderley et al 2008), Myh4 expression was expressed at significantly lower levels (28.82-fold reduction) in muscles taken from adult mice with the mini-muscle phenotype (Burniston et al 2013). This change was accompanied by additional expression differences in structural genes [e.g., myocyte enhancer factor 2C (Mef2c), 2-fold greater in mini-muscle samples] and myogenic factors [e.g., myogenin (Myog), 3.8-fold greater in mini-muscle] associated with slow-type myofibrils.…”

Section: Discussionsupporting

confidence: 59%

“…Transcriptional profiling of muscle shows a significant reduction in expression of Myh4 in Myh4 Minimsc relative to wild type Previously, genome-wide expression profiling described transcriptome differences in the medial gastrocnemius between HR mice (generation 37) with the mini-muscle phenotype (line 3) and HR mice with wild-type muscles (lines 7 and 8) (Burniston et al 2013). Differential expression analysis revealed that, consistent with the known reduction of type IIB fibers (Guderley et al 2008), Myh4 expression was expressed at significantly lower levels (28.82-fold reduction) in muscles taken from adult mice with the mini-muscle phenotype (Burniston et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Although other examples exist (see Stinchcombe et al 2009), we feel the discovery and subsequent identification of this mutation will provide an opportunity to more thoroughly examine the role of GOMEs in the response to selection. Another benefit of identifying a GOME in the context of this particular selection experiment is that we have a plethora of data on traits other than the selected phenotype (voluntary wheel running) (see references in Garland et al 2011b;Burniston et al 2013). This will enable us to better understand how the mutation has affected and might affect variation in related suborganismal traits related to voluntary wheel running.…”

Section: Evolutionary Significance Of Myh4 Minimscmentioning

confidence: 99%

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A Novel Intronic Single Nucleotide Polymorphism in the Myosin heavy polypeptide 4 Gene Is Responsible for the Mini-Muscle Phenotype Characterized by Major Reduction in Hind-Limb Muscle Mass in Mice

et al. 2013

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Replicated artificial selection for high levels of voluntary wheel running in an outbred strain of mice favored an autosomal recessive allele whose primary phenotypic effect is a 50% reduction in hind-limb muscle mass. Within the High Runner (HR) lines of mice, the numerous pleiotropic effects (e.g., larger hearts, reduced total body mass and fat mass, longer hind-limb bones) of this hypothesized adaptive allele include functional characteristics that facilitate high levels of voluntary wheel running (e.g., doubling of mass-specific muscle aerobic capacity, increased fatigue resistance of isolated muscles, longer hind-limb bones). Previously, we created a backcross population suitable for mapping the responsible locus. We phenotypically characterized the population and mapped the Minimsc locus to a 2.6-Mb interval on MMU11, a region containing 100 known or predicted genes. Here, we present a novel strategy to identify the genetic variant causing the mini-muscle phenotype. Using high-density genotyping and whole-genome sequencing of key backcross individuals and HR mice with and without the mini-muscle mutation, from both recent and historical generations of the HR lines, we show that a SNP representing a C-to-T transition located in a 709-bp intron between exons 11 and 12 of the Myosin heavy polypeptide 4 (Myh4) skeletal muscle gene (position 67,244,850 on MMU11; assembly, December 2011, GRCm38/mm10; ENSMUSG00000057003) is responsible for the mini-muscle phenotype, Myh4 Minimsc . Using next-generation sequencing, our approach can be extended to identify causative mutations arising in mouse inbred lines and thus offers a great avenue to overcome one of the most challenging steps in quantitative genetics.

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