Mutational analysis of TSC1 and TSC2 in Danish patients with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in the skin and other organs, including brain, heart, lung, kidney and bones. TSC is caused by mutations in TSC1 and TSC2. Here, we present the TSC1 and TSC2 variants identified in 168 Danish individuals out of a cohort of 327 individuals suspected of TSC.

Pre-conceptional exposure to multiwalled carbon nanotubes suppresses antibody production in mouse offspring.

Prenatal particle exposure has been shown to increase allergic responses in offspring. Carbon nanotubes (CNTs) possess immunomodulatory properties, but it is unknown whether maternal exposure to CNTs interferes with offspring immune development. Here, C57Bl/6J female mice were intratracheally instilled with 67 of μg multiwalled CNTs on the day prior to mating.

TSC1 and TSC2 regulate cilia length and canonical Hedgehog signaling via different mechanisms.

Primary cilia are sensory organelles that coordinate multiple cellular signaling pathways, including Hedgehog (HH), Wingless/Int (WNT) and Transforming Growth Factor-β (TGF-β) signaling. Similarly, primary cilia have been implicated in regulation of mTOR signaling, in which Tuberous Sclerosis Complex proteins 1 and 2 (TSC1/2) negatively regulate protein synthesis by inactivating the mTOR complex 1 (mTORC1) at energy limiting states. Here we report that TSC1 and TSC2 regulate Smoothened (SMO)-dependent HH signaling in mouse embryonic fibroblasts (MEFs).

Development of hypomelanotic macules is associated with constitutive activated mTORC1 in tuberous sclerosis complex.

TSC1 and TSC2 are genes mutated in the syndrome TSC (tuberous sclerosis complex). We describe a 3-generation family with 17 affected members, all presenting classic TSC features except renal manifestations. The disease segregates with a silent substitution in TSC2, c.

The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation.

The KDM5 family of histone demethylases removes the H3K4 tri-methylation (H3K4me3) mark frequently found at promoter regions of actively transcribed genes and is therefore generally considered to contribute to corepression. In this study, we show that knockdown (KD) of all expressed members of the KDM5 family in white and brown preadipocytes leads to deregulated gene expression and blocks differentiation to mature adipocytes. KDM5 KD leads to a considerable increase in H3K4me3 at promoter regions; however, these changes in H3K4me3 have a limited effect on gene expression per se.