Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12
dc.contributor.author | Shou, W. N. | en_US |
dc.contributor.author | Aghdasi, B. | en_US |
dc.contributor.author | Armstrong, D. L. | en_US |
dc.contributor.author | Guo, Q. X. | en_US |
dc.contributor.author | Bao, S. D. | en_US |
dc.contributor.author | Charng, M. J. | en_US |
dc.contributor.author | Mathews, L. M. | en_US |
dc.contributor.author | Schneider, Michael D. | en_US |
dc.contributor.author | Hamilton, S. L. | en_US |
dc.contributor.author | Matzuk, M. M. | en_US |
dc.date.accessioned | 2009-06-01T17:32:14Z | |
dc.date.available | 2009-06-01T17:32:14Z | |
dc.date.issued | 1998-01-29 | en_US |
dc.identifier.citation | Shou, WN; Aghdasi, B; Armstrong, DL; Guo, QX; Bao, SD; Charng, MJ; Mathews, LM; Schneider, MD; Hamilton, SL; Matzuk, MM. (1998) "Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12." Nature 391(6666): 489-492. <http://hdl.handle.net/2027.42/62697> | en_US |
dc.identifier.issn | 0028-0836 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/62697 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=9461216&dopt=citation | en_US |
dc.description.abstract | FKBP12, a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin, is ubiquitously expressed and interacts with proteins in several intracellular signal transduction systems(1). Although FKBP12 interacts with the cytoplasmic domains of type I receptors of the transforming growth factor-beta (TGF-beta) superfamily in vitro, the function of FKBP12 in TGF-beta superfamily signalling is controversial(2-6). FKBP12 also physically interacts stoichiometrically with multiple intracellular calcium release channels including the tetrameric skeletal muscle ryanodine dine receptor (RyR1)(7,8). In contrast, the cardiac ryanodine receptor, RyR2, appears to bind selectively the FKBP12 homologue, FKBP12.6 (refs 9, 10). To define the functions of FKBP12 in vivo, we generated mutant mice deficient in FKBP12 using embryonic stem (ES) cell technology. FKBP12-deficient mice have normal skeletal muscle but have severe dilated cardiomyopathy and ventricular septal defects that mimic a human congenital heart disorder, noncompaction of left ventricular myocardium(11,12). About 9% of the mutants exhibit exencephaly secondary to a defect in neural tube closure. Physiological studies demonstrate that FKBP12 is dispensable for TGF-beta-mediated signalling, but modulates the calcium release activity of both skeletal and cardiac ryanodine receptors. | en_US |
dc.format.extent | 850655 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/octet-stream | |
dc.format.mimetype | text/plain | |
dc.publisher | Macmillan Magazines Ltd. | en_US |
dc.source | Nature | en_US |
dc.title | Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12 | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationother | Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA | en_US |
dc.contributor.affiliationother | Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA | en_US |
dc.contributor.affiliationother | Baylor Coll Med, Dept Mol & Human Geneet, Houston, TX 77030 USA | en_US |
dc.contributor.affiliationother | Baylor Coll Med, Dept Physiol & Mol Biophys, Houston, TX 77030 USA | en_US |
dc.contributor.affiliationother | Baylor Coll Med, Dept Med, Houston, TX 77030 USA | en_US |
dc.identifier.pmid | 9461216 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/62697/1/391489a0.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1038/35146 | en_US |
dc.identifier.source | Nature | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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