M-creatine kinase gene expression in mechanically overloaded skeletal muscle of transgenic mice

1995 ◽  
Vol 269 (3) ◽  
pp. C665-C674 ◽  
Author(s):  
R. W. Tsika ◽  
S. D. Hauschka ◽  
L. Gao
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Muscle Creatine Kinase ◽  
Kinase Gene ◽  
Mouse Muscle ◽  
Average Decrease ◽  
Mechanical Overload ◽  
Mouse Lines ◽  
Specific Mrna

The molecular pathways and regulatory molecules that underlie changes in gene transcription during mechanical overload of skeletal muscle remain obscure. To better understand this process, we have examined mouse muscle creatine kinase (MCK) gene expression in mechanically overloaded plantaris (OP) muscle of transgenic and nontransgenic mice. Northern blot analysis revealed that endogenous MCK-specific mRNA transcripts were decreased 150% in the OP muscles after 6 wk. To identify the MCK gene regions involved in the response to mechanical overload, three different mouse MCKCAT transgenes were studied by measuring chloramphenicol acetyltransferase (CAT assays) activity in OP and sham-operated (control plantaris) muscles. Mouse lines carrying (+enh206)117MCKCAT and -1256MCKCAT transgenes exhibited 30 and 40% lower CAT levels, whereas two mouse lines carrying -3300MCKCAT transgenes exhibited average decreases of 430%. Nearly identical results, including measurements of exogenous CAT mRNA, were obtained 2 days postoverload. Six weeks or 2 days of mechanical overload led to an average decrease in MM-CK isoprotein of 140%. These data provide evidence that mechanical overload induces changes in MCK gene expression that appear to be regulated by at least two portions of the MCK gene: the 206 base pair 5' enhancer and the -3,300 to -1,257 region.

Genotypes Of The Skeletal Muscle Creatine Kinase Gene And Exertional Rhabdomyolyis

2009 ◽  
Vol 41 ◽  
pp. 164
Author(s):  
Yuval Heled ◽  
Patricia A. Deuster ◽  
Sheila Muldoon ◽  
Carmen Sesvold-Contreras ◽  
Kimbra Kenny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Muscle Creatine Kinase ◽  
Kinase Gene ◽  
Muscle Creatine

Developmental regulation of creatine kinase gene expression by myogenic factors in embryonic mouse and chick skeletal muscle

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 1017-1029 ◽  
Author(s):  
G.E. Lyons ◽  
S. Muhlebach ◽  
A. Moser ◽  
R. Masood ◽  
B.M. Paterson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Striated Muscle ◽  
Myogenic Differentiation ◽  
Developmental Regulation ◽  
Specific Gene ◽  
Kinase Gene ◽  
Embryonic Mouse ◽  
Myogenic Factors

The B isoform of creatine kinase (BCK), which is expressed at a high level in embryonic neural tissues, is also expressed abundantly in developing striated muscle and is an early marker for skeletal myogenesis. Using isoform-specific 35S-labeled antisense cRNA probes for in situ hybridization, we have detected BCK mRNAs in embryonic mouse and chick myotomes, the first skeletal muscle masses to form in developing embryos. These transcripts are detectable as soon as myotomes are morphologically distinguishable. BCK is expressed at high levels in both skeletal and cardiac muscle in mouse and chick embryos. In the mouse, BCK transcript levels fall of rapidly in striated muscle shortly after the onset of MCK gene expression. The M isoform of creatine kinase (MCK), the striated muscle-specific isoform, is expressed later than BCK. In the mouse, BCK transcripts are expressed in myotomes at 8.5 days post coitum (p.c.), but MCK transcripts are not detected before 13 days p.c. In the chick, BCK mRNAs are present at Hamburger-Hamilton stage 13, but MCK mRNAs are not detected before stage 19. We have compared the patterns of expression of the CK genes with those of myogenic differentiation factor genes, which are thought to regulate skeletal muscle-specific gene expression. In the chick, both CMD1, first detected at stage 13, and myogenin, first detected at stage 15, are present prior to MCK, which begins to be expressed at stage 19. Unlike the mouse embryo, CMD1, the chick homologue of MyoD1, is expressed before chick myogenin. In the mouse, myogenin, first detected at 8.5 days p.c., is expressed at the same time as BCK in myotomes. Both myogenin and MyoD1, which begins to be detected two days later than myogenin, are expressed at least two days before MCK. It has been proposed that the myogenic factors, MyoD1 and myogenin, directly regulate MCK gene expression in the mouse by binding to its enhancer. However, our results show that MCK transcripts are not detected until well after MyoD1 and myogenin mRNAs are expressed, suggesting that these factors by themselves are not sufficient to initiate MCK gene expression.

The mouse muscle creatine kinase promoter faithfully drives reporter gene expression in transgenicXenopus laevis

2004 ◽  
Vol 18 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Wayland Lim ◽  
Eric S. Neff ◽  
J. David Furlow
Keyword(s):  
Gene Expression ◽  
Creatine Kinase ◽  
Transgene Expression ◽  
Muscle Development ◽  
Fluorescent Protein ◽  
Regulatory Sequences ◽  
Gene Promoters ◽  
Muscle Creatine Kinase ◽  
Mouse Muscle ◽  
Muscle Creatine

Developing Xenopus laevis experience two periods of muscle differentiation, once during embryogenesis and again at metamorphosis. During metamorphosis, thyroid hormone induces both muscle growth in the limbs and muscle death in the tail. In mammals, the muscle creatine kinase (MCK) gene is activated during the differentiation from myoblasts to myocytes and has served as both a marker for muscle development and to drive transgene expression in transgenic mice. Transcriptional control elements are generally highly conserved throughout evolution, potentially allowing mouse promoter use in transgenic X. laevis. This paper compares endogenous X. laevis MCK gene expression and the mouse MCK (mMCK) promoter driving a green fluorescent protein reporter in transgenic X. laevis. The mMCK promoter demonstrated strong skeletal muscle-specific transgene expression in both the juvenile tadpole and adult frog. Therefore, our results clearly demonstrate the functional conservation of regulatory sequences in vertebrate muscle gene promoters and illustrate the utility of using X. laevis transgenesis for detailed comparative study of mammalian promoter activity in vivo.

scholarly journals Analysis of muscle creatine kinase gene regulatory elements in skeletal and cardiac muscles of transgenic mice.

1996 ◽  
Vol 16 (4) ◽  
pp. 1649-1658 ◽  
Author(s):  
D B Donoviel ◽  
M A Shield ◽  
J N Buskin ◽  
H S Haugen ◽  
C H Clegg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Transgenic Mice ◽  
Cardiac Muscle ◽  
Muscle Cells ◽  
Regulatory Elements ◽  
Muscle Creatine Kinase ◽  
Regulatory Regions ◽  
Mouse Muscle ◽  
Muscle Creatine

Regulatory regions of the mouse muscle creatine kinase (MCK) gene, previously discovered by analysis in cultured muscle cells, were analyzed in transgenic mice. The 206-bp MCK enhancer at nt-1256 was required for high-level expression of MCK-chloramphenicol acetyltransferase fusion genes in skeletal and cardiac muscle; however, unlike its behavior in cell culture, inclusion of the 1-kb region of DNA between the enhancer and the basal promoter produced a 100-fold increase in skeletal muscle activity. Analysis of enhancer control elements also indicated major differences between their properties in transgenic muscles and in cultured muscle cells. Transgenes in which the enhancer right E box or CArG element were mutated exhibited expression levels that were indistinguishable from the wild-type transgene. Mutation of three conserved E boxes in the MCK 1,256-bp 5' region also had no effect on transgene expression in thigh skeletal muscle expression. All these mutations significantly reduced activity in cultured skeletal myocytes. However, the enhancer AT-rich element at nt - 1195 was critical for expression in transgenic skeletal muscle. Mutation of this site reduced skeletal muscle expression to the same level as transgenes lacking the 206-bp enhancer, although mutation of the AT-rich site did not affect cardiac muscle expression. These results demonstrate clear differences between the activity of MCK regulatory regions in cultured muscles cells and in whole adult transgenic muscle. This suggests that there are alternative mechanism of regulating the MCK gene in skeletal and cardiac muscle under different physiological states.

The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer

1988 ◽  
Vol 8 (1) ◽  
pp. 62-70
Author(s):  
J B Jaynes ◽  
J E Johnson ◽  
J N Buskin ◽  
C L Gartside ◽  
S D Hauschka
Keyword(s):  
Creatine Kinase ◽  
Cultured Cells ◽  
Simian Virus 40 ◽  
Regulatory Elements ◽  
Simian Virus ◽  
Major Influence ◽  
Transcriptional Enhancer ◽  
Muscle Creatine Kinase ◽  
Kinase Gene ◽  
Muscle Creatine

Muscle creatine kinase (MCK) is induced to high levels during skeletal muscle differentiation. We have examined the upstream regulatory elements of the mouse MCK gene which specify its activation during myogenesis in culture. Fusion genes containing up to 3,300 nucleotides (nt) of MCK 5' flanking DNA in various positions and orientations relative to the bacterial chloramphenicol acetyltransferase (CAT) structural gene were transfected into cultured cells. Transient expression of CAT was compared between proliferating and differentiated MM14 mouse myoblasts and with nonmyogenic mouse L cells. The major effector of high-level expression was found to have the properties of a transcriptional enhancer. This element, located between 1,050 and 1,256 nt upstream of the transcription start site, was also found to have a major influence on the tissue and differentiation specificity of MCK expression; it activated either the MCK promoter or heterologous promoters only in differentiated muscle cells. Comparisons of viral and cellular enhancer sequences with the MCK enhancer revealed some similarities to essential regions of the simian virus 40 enhancer as well as to a region of the immunoglobulin heavy-chain enhancer, which has been implicated in tissue-specific protein binding. Even in the absence of the enhancer, low-level expression from a 776-nt MCK promoter retained differentiation specificity. In addition to positive regulatory elements, our data provide some evidence for negative regulatory elements with activity in myoblasts. These may contribute to the cell type and differentiation specificity of MCK expression.

A ras-dependent pathway abolishes activity of a muscle-specific enhancer upstream from the muscle creatine kinase gene

1989 ◽  
Vol 9 (2) ◽  
pp. 594-601
Author(s):  
E A Sternberg ◽  
G Spizz ◽  
M E Perry ◽  
E N Olson
Keyword(s):  
Creatine Kinase ◽  
Growth Factors ◽  
Myogenic Differentiation ◽  
Regulatory Elements ◽  
Negative Control ◽  
Proximal Promoter ◽  
Muscle Creatine Kinase ◽  
Kinase Gene ◽  
Muscle Creatine ◽  
Ras Oncogenes

Differentiation of skeletal myoblasts is accompanied by induction of a series of tissue-specific genes whose products are required for the specialized functions of the mature muscle fiber. The program for myogenic differentiation is subject to negative control by several peptide growth factors and by the products of mutationally activated ras oncogenes, which persistently activate intracellular cascades normally triggered by specific growth factors. Previously, we reported that induction of the muscle creatine kinase (mck) gene during myogenesis was dependent on a distal upstream enhancer that cooperated with a proximal promoter to direct high levels of expression in developing muscle cells (E. A. Sternberg, G. Spizz, W. M. Perry, D. Vizard, T. Weil, and E. N. Olson, Mol. Cell. Biol. 8:2896-2909). To investigate the mechanisms whereby ras blocks the induction of muscle-specific genes, we have examined the ability of mck 5' regulatory elements to direct expression of the linked reporter gene for chloramphenicol acetyltransferase (cat) in C2 myoblasts bearing mutant N-ras and H-ras oncogenes. In this paper we report that expression of activated ras alleles abolishes activity of the mck upstream enhancer but does not affect the activity of the mck promoter. The ability of ras to repress the expression of mck-cat fusion genes that have been transfected either transiently or stably into myoblasts suggests that ras may exert its effects on muscle-specific genes through mechanisms independent of chromatin configurations or DNA methylation. These results also suggest that ras blocks establishment of the myogenic phenotype by preventing the accumulation of regulatory factors required for transcriptional induction of muscle-specific genes.

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