Module 12: Figure FKBP12.6 deletion induces hypertrophy

Deletion of FK506-binding protein 12.6 (FKBP12.6) results in an increase in the amplitude of the Ca2+ transient.

In transgenic mice where the FK506-binding protein 12.6 (FKBP12.6) protein has been deleted, the onset of hypertrophy is associated with a marked increase in the amplitude of the Ca2+ transient. This increase in amplitude results from an increase in the amount of Ca2+ released from the sarcoplasmic reticulum (SR). As shown in the lower current traces, there was no change in the influx of Ca2+ across the plasma membrane, indicating that the increase in amplitude is due to the ryanodine receptor 2 (RYR2) channels opening for longer to increase the amount of released Ca2+. Of particular interest was the observation that the hypertrophy occurred only in the males. The females appear to be protected by oestrogen, because they did develop hypertrophy when treated with tamoxifen, an oestrogen receptor antagonist. Reproduced by permission from Macmillan Publishers Ltd: Nature, Xin, H.-B., Senbonmatsu, T., Cheng, D.-S., Wang, Y.-X., Copello, J.A., Ji, G.-J., Collier, M.L., Deng, K.-Y., Jeyakumar, L.H., Magnuson, M.A., Inagami, T., Kotlikoff, M.I. and Fleischer, S. (2002) Oestrogen protects FKBP12.6 null mice from cardiac hypertrophy. 416:334–338. Copyright (2002);; see Xin et al. 2002.