Decreased glucocerebrosidase activity and substrate accumulation of glycosphingolipids in a novel GBA1 D409V knock-in mouse model.

Multiple mutations have been described in the human GBA1 gene, which encodes the lysosomal enzyme beta-glucocerebrosidase (GCase) that degrades glucosylceramide and is pivotal in glycosphingolipid substrate metabolism. Depletion of GCase, typically by homozygous mutations in GBA1, is linked to the lysosomal storage disorder Gaucher's disease (GD) and distinct or heterozygous mutations in GBA1 are associated with increased Parkinson's disease (PD) risk. While numerous genes have been linked to heritable PD, GBA1 mutations in aggregate are the single greatest risk factor for development of idiopathic PD.

The transgenic mouse: a new model to delineate platelet and leukocyte functions.

Conditional knockout (KO) mouse models are invaluable for elucidating the physiological roles of platelets. The () transgenic mouse is the current model of choice for generating megakaryocyte/platelet-specific KO mice. Platelets and leukocytes work closely together in a wide range of disease settings, yet the specific contribution of platelets to these processes remains unclear.

Endothelial and macrophage-specific deficiency of P38α MAPK does not affect the pathogenesis of atherosclerosis in ApoE-/- mice.

Background: The p38α Mitogen-Activated Protein Kinase (MAPK) regulates stress- and inflammation-induced cellular responses. Factors implicated in the development of atherosclerosis including modified low-density lipoprotein (LDL), cytokines and even shear stress induce p38 activation in endothelial cells and macrophages, which may be important for plaque formation. This study investigates the effects of endothelial- and macrophage-specific deficiency of p38α in atherosclerosis development, in Apolipoprotein E deficient (ApoE(-/-)) mice.

GFP-p65 knock-in mice as a tool to study NF-kappaB dynamics in vivo.

The nuclear factor kappaB (NF-kappaB) signaling pathway regulates immune and inflammatory responses and is implicated in the pathogenesis of multiple diseases. The principal mechanism controlling NF-kappaB activation depends on the association of NF-kappaB transcription factor dimers with IkappaB molecules, which prevents the accumulation of NF-kappaB in the nucleus and the activation of target gene transcription. Monitoring the nucleocytoplalsmic shuttling of NF-kappaB factors is a reliable method to study the dynamic regulation of NF-kappaB activity.

Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis.

Atherosclerosis is a progressive disorder of the arterial wall and the underlying cause of cardiovascular diseases such as heart attack and stroke. Today, atherosclerosis is recognized as a complex disease with a strong inflammatory component. The nuclear factor-kappaB (NF-kappaB) signaling pathway regulates inflammatory responses and has been implicated in atherosclerosis.