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XB-ART-35218
Dev Biol April 1, 2007; 304 (1): 260-71.

Changing a limb muscle growth program into a resorption program.

Cai L , Das B , Brown DD .


Abstract
Transgenic Xenopus laevis tadpoles that express a dominant negative form of the thyroid hormone receptor (TRDN) controlled by the cardiac actin muscle promoter (pCar) develop with very little limb muscle. Under the control of the tetracycline system the transgene can be induced at will by adding doxycycline to the rearing water. Pre-existing limb muscle fibers begins to disintegrate within 2 days after up-regulation of the TRDN transgene. The muscle cells do not die even after weeks of transgene exposure when the myofibrils have degenerated completely and the tadpole is nearing death. A microarray analysis after 2 weeks of exposure to the transgene identified 24 muscle genes whose expression was altered in such a way that they might cause the muscle phenotype. These candidate genes are normally activated in growing limb muscle but they are repressed by the TRDN transgene. Several of these genes have been implicated in mammalian myopathies. However, the expression of only one of these genes, calsequestrin, is down-regulated in 1 day and therefore might initiate the degeneration. Calsequestrin is one of several affected genes that encode proteins involved in calcium sequestration, transport and utilization in muscle suggesting that uncontrolled calcium influx into the growing limb muscle fibers causes rhabdomyolysis. Many of the same genes that are down-regulated in the tail at the peak of metamorphic climax just before it is resorbed are suppressed in the transgenic limb muscle in effect turning the limb growth program into a tail resorption program.

PubMed ID: 17234173
PMC ID: PMC1868508
Article link: Dev Biol
Grant support: [+]
Genes referenced: acta1 actc1 actl6a aldoa art1 atp2a1 bin1 cacng6 casq1 chdh chrna1 chrnd chrne ckm dan4l eef1a2 eno3 frs3 ldb3 ldha mmp15 myh1 myh2 myh4 myoz1 pdhb pdlim7 pfkm pgam2 pgk1 phka1 phkg1 ppp2r3a ryr1 ryr3 sirt1 slc25a4 slc41a3 thbs3 tnnc2 tnni2 tpi1 tpm2 trdn ttn XB5727854 [provisional]
Antibodies: Fast Skeletal Muscle Ab2

GEO Series:
   GSE5249: NCBI


Article Images: [+] show captions
References [+] :
Batt, Differential gene expression profiling of short and long term denervated muscle. 2006, Pubmed


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