THE EXPRESSION OF MDM2 AND OTHER P53-REGULATED PROTEINS IN THE TISSUES OF THE DEVELOPING RAT

The expression of MDM2 was monitored in tissues taken from rats at dif ferent stages of development. Two major protein species of 90K and 130 K were identified, although expression was not the same in all tissues . In most the level of the larger protein tended to decrease as the fo etus developed, being relatively scarce after birth. The expression of the 90K product (usually considered to be the major MDM2 protein), ho wever, increased as the animals developed, being most abundant in adul t tissues, suggesting that the two proteins play quite different roles during development. p53 expression mirrored that of the smaller MDM2 protein in most, but not all, tissues. This is consistent with previou s suggestions made on the basis of in vitro studies that expression of the latter protein is regulated by p53. In addition, the level of two other p53-regulated proteins, Bcl-2 and Bax, were examined. In most t issues expression of both proteins decreased as the foetus developed, being virtually undetectable in adults. These data strongly suggest th at factors other than p53 exert the major influence over Bcl-2 and Bax expression, although levels of the 90K MDM2 protein are more likely t o be regulated by p53. However, it was noted that the levels of MDM2 i n the tissues of p53-null mice were comparable to those seen in the no rmal rat.