Activation of Endogenous Retroviruses in Dnmt1(-/-) ESCs Involves Disruption of SETDB1-Mediated Repression by NP95 Binding to Hemimethylated DNA.

Repression of endogenous retroviruses (ERVs) in mammals involves several epigenetic mechanisms. Acute loss of the maintenance methyltransferase Dnmt1 induces widespread DNA demethylation and transcriptional activation of ERVs, including CpG-rich IAP (intracisternal A particle) proviruses. Here, we show that this effect is not due simply to a loss of DNA methylation.

Nucleotide-sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human.

Proteoglycans are a family of extracellular macromolecules comprised of glycosaminoglycan chains of a repeated disaccharide linked to a central core protein. Proteoglycans have critical roles in chondrogenesis and skeletal development. The glycosaminoglycan chains found in cartilage proteoglycans are primarily composed of chondroitin sulfate.

Neuronal and glial accumulation of alpha- and beta-synucleins in human lipidoses.

A number of the lysosomal storage diseases that have now been characterized are associated with intra-lysosomal accumulation of lipids, caused by defective lysosomal enzymes. We have previously reported neuronal accumulation of both alpha- and beta-synucleins in brain tissue of a GM2 gangliosidosis mouse model. Although alpha-synuclein has been implicated in several neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, its functions remain largely unclear.

Possible role of autoantibodies in the pathophysiology of GM2 gangliosidoses.

Mice containing a disruption of the Hexb gene have provided a useful model system for the study of the human lysosomal storage disorder known as Sandhoff disease (SD). Hexb(-/-) mice rapidly develop a progressive neurologic disease of ganglioside GM2 and GA2 storage. Our study revealed that the disease states in this model are associated with the appearance of antiganglioside autoantibodies.

Plasmid-based gene transfer ameliorates visceral storage in a mouse model of Sandhoff disease.

Sandhoff disease is a severe neurodegenerative disorder with visceral involvement caused by mutations in the HEXB gene coding for the beta subunit of the lysosomal hexosaminidases A and B. HEXB mutations result in the accumulation of undegraded substrates such as GM2 and GA2 in lysosomes. We evaluated the efficacy of cationic liposome-mediated plasmid gene therapy using the Sandhoff disease mouse, an animal model of a human lysosomal storage disease.

Neuronal accumulation of alpha- and beta-synucleins in the brain of a GM2 gangliosidosis mouse model.

Sandhoff disease (SD) is a heritable lysosomal storage disease resulting from impaired degradation of GM2 ganglioside. The hallmark pathology of the SD model mouse brain is GM2 ganglioside accumulation in neurons. In the present study, we immunohistochemically investigated the neuronal pathology in SD mouse brains, and demonstrated neuronal accumulation of alpha- and beta-synucleins in addition to GM2 ganglioside.