Distribution of Tsc1 protein detected by immunohistochemistry in various normal rat tissues and the renal carcinomas of Eker rat: Detection of limited colocalization with Tsc1 and Tsc2 gene products in vivo

We and others previously demonstrated that hereditary mutation and a subseq uent second hit in the rat homolog of tuberous sclerosis gene (Tsc2) are re sponsible for Eker renal carcinomas (RC). in humans, alteration in the TSC2 gene is known to cause the tuberous sclerosis complex (TSC) that results i n hamartomatous lesions in multiple organs, but the function of TSC2 is not fully understood. In recent years, a second gene (TSC1) responsible for hu man TSC has been cloned, and binding between TSC1 and TSC2 proteins was rep orted. In this study, to clarify associations between Tsc proteins in vivo, the expression of Tsc1 protein was detected by immunohistochemistry, and c ompared with Tsc2 expression. Tsc1 protein was expressed in the nervous sys tem and in many endocrine tissues, including pancreatic islets, the parathy roids, testis, and ovary. Tsc1 was also detected in the many epithelial tis sues of organs, such as kidney, uterus, small and large intestine, and live r. Our results indicate overlapping, but not identical, organ distributions of Tsc1 and Tsc2 proteins. At the intracellular distribution, double fluor escent immunolabeling allowed the determination that only a partial portion of Tsc1 signals overlapped with Tsc2 in some organs. These results suggest the existence of co-localizing and independent forms of Tsc proteins in en dogenous expressions. Additionally, relatively high expression of Tsc1 prot ein was detected in RC in the Tsc2 mutant (Eker) rat.