+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Developmental expression of the tuberous sclerosis proteins tuberin and hamartin

Developmental expression of the tuberous sclerosis proteins tuberin and hamartin

Acta Neuropathologica 101(3): 202-210

Tuberous sclerosis complex is an autosomal dominant multisystem disorder, characterized 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 antibodies for hamartin and tuberin, we analyzed the expression of these two proteins by Western blot analyses in normal developing human and rat tissues. Both 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 characterize the developmental expression of tuberin and hamartin, we conducted a detailed study in rat tissues from embryonic day 13 to adult by Western blot analysis and immunohistochemistry. Immunohistochemical staining of rat tissues for tuberin and hamartin revealed tissue-specific expression patterns throughout development. Both tuberin and hamartin are expressed in epithelia, muscle (smooth, cardiac and skeletal muscle) and the nervous system (neurons, glia, choroid plexus and arachnoid). Except for the central nervous system, immunostaining intensity declines with age, confirming the protein blot analysis. These results indicate that tuberin and hamartin may play a critical role in development, and thus provide a framework for understanding the developmental and hamartomatous manifestations of tuberous sclerosis. These findings also suggest that tuberin and hamartin have additional functions in the adult brain, consistent with the marked neurological problems that afflict many patients with tuberous sclerosis.

(PDF emailed within 0-6 h: $19.90)

Accession: 010452398

Download citation: RISBibTeXText

PMID: 11307618

DOI: 10.1007/s004010000269

Related references

Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis. Journal of Biological Chemistry 276(24): 21017-21021, 2001

Tuberous Sclerosis: Immunohistochemistry Expression Of Tuberin And Hamartin In A 31-Week Gestational Fetus. Fetal & Pediatric Pathology 23(4): 241-249, 2004

Loss of expression of tuberin and hamartin in tuberous sclerosis complex-associated but not in sporadic angiofibromas. Journal of Cutaneous Pathology 30(3): 174-177, 2003

Tuberous sclerosis: immunohistochemistry expression of tuberin and hamartin in a 31-week gestational fetus. Fetal and Pediatric Pathology 23(4): 241-249, 2005

Distribution between monomeric and heteromeric forms of tuberin in association with hamartin, two proteins involved in tuberous sclerosis. Journal of Investigative Medicine 48(1): 80A, 2000

The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting partners. Mutation Research 658(3): 234-246, 2008

Expression of the tuberous sclerosis complex gene products, hamartin and tuberin, in central nervous system tissues. Acta Neuropathologica 99(3): 223-230, 2000

A case of intractable epilepsy: diagnosis of tuberous sclerosis based on histopathological findings and immunohistochemical expression of hamartin and tuberin. No to Hattatsu. Brain and Development 34(1): 49-54, 2002

Expression of tuberin and hamartin in tuberous sclerosis complex-associated and sporadic cortical dysplasia of Taylor's balloon cell type. Folia Neuropathologica 46(1): 43-48, 2008

Tuberin and hamartin expression is reduced in the majority of subependymal giant cell astrocytomas in tuberous sclerosis complex consistent with a two-hit model of pathogenesis. Journal of Child Neurology 19(2): 102-106, 2004

Tuberous sclerosis complex: Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms. Pathology, Research and Practice 212(11): 972-979, 2016

Multicompartmental distribution of the tuberous sclerosis gene products, hamartin and tuberin. Archives of Biochemistry & Biophysics 404(2): 210-217, August 15, 2002

Simultaneous loss of hamartin and tuberin from the cerebrum, kidney and heart with tuberous sclerosis. Acta Neuropathologica 99(5): 503-510, 2000

Tuberous sclerosis in a 19-week fetus: immunohistochemical and molecular study of hamartin and tuberin. Pediatric and Developmental Pathology 5(5): 448-464, 2002

Cellular co-localization of hamartin and tuberin and early hamartoma formation in tuberous sclerosis. Laboratory Investigation 82(1): 314A, 2002