Identification of the sites of expression of triple A syndrome mRNA in the rat using in situ hybridisation.

Triple A syndrome is characterised by achalasia, alacrima, adrenocorticotropin-resistant adrenal insufficiency and a variable and progressive neurological phenotype. It is caused by mutations in a gene that is normally referred to as the triple A syndrome gene (AAAS) and which has recently been shown to encode a nuclear pore protein named ALADIN (alacrima, achalasia, adrenal insufficiency neurologic disorder). In this study we performed in situ hybridisation with radioactive oligonucleotide probes in the adult and developing rat and present the first detailed map of AAAS mRNA expression. Consistent with a role for AAAS in adrenal function, we detected high levels of its mRNA in the adrenal cortex. On the other hand hepatocytes, enteric smooth muscle and fibroblasts had relatively little or no detectable AAAS mRNA. In both the peripheral and central nervous systems, AAAS mRNA was abundantly expressed. Neurons in sensory and sympathetic ganglia expressed high levels. CNS expression was highest in neurons of the cerebral cortex, cerebellum, hippocampus, motor-associated nuclei of the brainstem including cranial nerve nuclei, and ventral horn of the spinal cord. Although neuronal expression of AAAS mRNA was striking, non-neuronal cells including those of the circumventricular organs and fibrous astrocytes also expressed AAAS mRNA. Within the developing embryo, the highest levels of expression were found in neural tissues. These findings indicate a widespread but not ubiquitous or uniform expression of AAAS mRNA in the rat. Robust expression in neural systems associated with cognitive, motor and sensory functions is consistent with the myriad of symptoms experienced by patients with triple A syndrome.