Imperial College London


Faculty of MedicineNational Heart & Lung Institute

Chair in Cardiology



+44 (0)013 34621727m.d.schneider Website




ICTEM buildingHammersmith Campus






BibTex format

author = {Shou, W and Aghdasi, B and Armstrong, DL and Guo, Q and Bao, S and Charng, MJ and Mathews, LM and Schneider, MD and Hamilton, SL and Matzuk, MM},
doi = {10.1038/35146},
journal = {Nature},
pages = {489--492},
title = {Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12.},
url = {},
volume = {391},
year = {1998}

RIS format (EndNote, RefMan)

AB - 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. 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. FKBP12 also physically interacts stoichiometrically with multiple intracellular calcium release channels including the tetrameric skeletal muscle ryanodine receptor (RyR1). In contrast, the cardiac ryanodine receptor, RyR2, appears to bind selectively the FKBP12 homologue, FKBP12.6. 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. 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.
AU - Shou,W
AU - Aghdasi,B
AU - Armstrong,DL
AU - Guo,Q
AU - Bao,S
AU - Charng,MJ
AU - Mathews,LM
AU - Schneider,MD
AU - Hamilton,SL
AU - Matzuk,MM
DO - 10.1038/35146
EP - 492
PY - 1998///
SN - 0028-0836
SP - 489
TI - Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12.
T2 - Nature
UR -
UR -
VL - 391
ER -