Developmental expression of the tuberous sclerosis proteins tuberin and hamartin

Tuberous sclerosis complex is an autosomal dominant multisystem disorder, c haracterized by the development of hamartomas in multiple organs, primarily the skin, heart, kidney, and brain. The tuberous sclerosis genes, TSC1 and TSC2, encode hamartin and tuberin, respectively. Employing specific antibo dies for hamartin and tuberin, we analyzed the expression of these two prot eins by Western blot analyses in normal developing human and rat tissues. B oth proteins are expressed ubiquitously in human fetal tissues and placenta , but are expressed at relatively low levels in human adult tissues, except brain. Similarly, high expression of these two proteins is observed in rat embryonic tissues, with a progressive decline after birth. To better chara cterize the developmental expression of tuberin and hamartin, we conducted a detailed study in rat tissues from embryonic day 13 to adult by Western b lot analysis and immunohistochemistry. Immunohistochemical staining of rat tissues for tuberin and hamartin revealed tissue-specific expression patter ns throughout development. Both tuberin and hamartin are expressed in epith elia, muscle (smooth, cardiac and skeletal muscle) and the nervous system ( neurons, glia, choroid plexus and arachnoid). Except for the central nervou s system, immunostaining intensity declines with age, confirming the protei n blot analysis. These results indicate that tuberin and hamartin may play a critical role in development, and thus provide a framework for understand ing the developmental and hamartomatous manifestations of tuberous sclerosi s. These findings also suggest that tuberin and hamartin have additional fu nctions in the adult brain, consistent with the marked neurological problem s that afflict many patients with tuberous sclerosis.