Fig. 11.

Working model. Tissue-specific disruption of angiotensinogen (Agt) has previously been performed using Cre-recombinase expressing lines that are assumed to be organ specific. Previous work using this approach led to the conclusion that liver (and adipose)-derived AGT is required for renal development and survival (38). The present study demonstrates that disruption of Agt in adrenal and brain tissue causes similar problems in renal development and survival and that Cre-recombinase driven by the albumin (Alb) promoter is unexpectedly active in adrenal gland. Similarly, the endogenous glial fibrillary acidic protein (Gfap) promoter is active in adrenal gland, prompting reconsideration of the mechanism by which expression of an angiotensin II (ANG II) transgene via this promoter rescues the lethality of global Agt knockout (37). Thus, these findings support the iconoclastic hypothesis that adrenal Agt (as opposed to hepatic-derived, circulating AGT protein) is required for renal development and survival, possibly through modulation of steroid synthesis and release. Ap2, adipocyte protein 2; Kap, kidney androgen response protein.