A phosphodiesterase 11 (Pde11a) knockout mouse expressed functional but reduced Pde11a: Phenotype and impact on adrenocortical function.

摘要: Phosphodiesterases catalyze the hydrolysis of cyclic nucleotides and maintain physiologic levels intracellular concentrations adenosine guanosine mono-phosphate (cAMP cGMP, respectively). Increased cAMP signaling has been associated with adrenocortical tumors Cushing syndrome. Genetic defects in phosphodiesterase 11A (PDE11A) may lead to increased have found predispose development adrenocortical, prostate, testicular tumors. A previously reported Pde11a knockout (Pde11a-/-) mouse line was studied express PDE11A mRNA protein still, albeit at reduced levels; functional studies various tissues showed activity. Since patients syndrome haploinsufficiency, it particularly pertinent study this hypomorphic line. Indeed, Pde11a-/- mice failed suppress corticosterone secretion response low dose dexamethasone, addition exhibited adrenal subcapsular hyperplasia predominant fetal-like features inner cortex, mimicking other models cortex. We conclude that a continuing expression function most tissues. Nevertheless, partial inactivation led an phenotype consistent what we see haploinsufficiency.