Search results for "MUTATION"
showing 10 items of 2830 documents
IgG1 B cell receptor signaling is inhibited by CD22 and promotes the development of B cells whose survival is less dependent on Ig alpha/beta.
2007
We describe a mouse strain in which B cell development relies either on the expression of membrane-bound immunoglobulin (Ig) gamma1 or mu heavy chains. Progenitor cells expressing gamma1 chains from the beginning generate a peripheral B cell compartment of normal size with all subsets, but a partial block is seen at the pro- to pre-B cell transition. Accordingly, gamma1-driven B cell development is disfavored in competition with developing B cells expressing a wild-type (WT) IgH locus. However, the mutant B cells display a long half-life and accumulate in the mature B cell compartment, and even though partial truncation of the Ig alpha cytoplasmic tail compromises their development, it does…
Genotoxicity of 1,4-benzoquinone and 1,4-naphthoquinone in relation to effects on glutathione and NAD(P)H levels in V79 cells.
1989
1,4-Benzoquinone is cytotoxic in V79 Chinese hamster cells and induces gene mutations and micronuclei. The cell-damaging effects of quinones are usually attributed to thiol depletion, oxidation of NAD(P)H, and redox-cycling involving the formation of semiquinone radicals and reactive oxygen species. To elucidate the role of these mechanisms in the genotoxicity of 1,4-benzoquinone, we measured various genotoxic effects, cytotoxicity, and the levels of glutathione, NADPH, NADH, and their oxidized forms all in the same experiment. 1,4-Naphthoquinone, which does not induce gene mutations in V79 cells, was investigated for comparative reasons. The quinones had a similar effect on the levels of c…
Differential regulation of the clusterin gene by Ha-ras and c-myc oncogenes and during apoptosis
1998
Clusterin (ApoJ) is an extracellular glycoprotein expressed during processes of tissue differentiation and regression that involve programmed cell death (apoptosis). Increased clusterin expression has also been found in tumors, however, the mechanism underlying this induction is not known. Apoptotic processes in tumors could be responsible for clusterin gene activation. Alternatively, oncogenic mutations could modulate signal transduction, thereby inducing the gene. We examined the response of the rat clusterin gene to two oncogenes, Ha-ras and c-myc, in transfected Rat1 fibroblasts. While c-myc overexpression did not modify clusterin gene activity, the Ha-ras oncogene produced a seven to t…
p53 as the main traffic controller of the cell signaling network
2010
Among different pathological conditions that affect human beings, cancer has received a great deal of attention primarily because it leads to significant morbidity and mortality. This is essentially due to increasing world-wide incidence of this disease and the inability to discover the cause and molecular mechanisms by which normal human cells acquire the characteristics that define cancer cells. Since the discovery of p53 over a quarter of a century ago, it is now recognized that virtually all cell fate pathways of live cells and the decision to die are under the control of p53. Such extensive involvement indicates that p53 protein is acting as a major traffic controller in the cell signa…
Mast Cell–deficient KitW-sh “Sash” Mutant Mice Display Aberrant Myelopoiesis Leading to the Accumulation of Splenocytes That Act as Myeloid-Derived S…
2013
Abstract Mast cell-deficient KitW-sh “sash” mice are widely used to investigate mast cell functions. However, mutations of c-Kit also affect additional cells of hematopoietic and nonimmune origin. In this study, we demonstrate that KitW-sh causes aberrant extramedullary myelopoiesis characterized by the expansion of immature lineage-negative cells, common myeloid progenitors, and granulocyte/macrophage progenitors in the spleen. A consistent feature shared by these cell types is the reduced expression of c-Kit. Populations expressing intermediate and high levels of Ly6G, a component of the myeloid differentiation Ag Gr-1, are also highly expanded in the spleen of sash mice. These cells are …
Two mutations in gB-1 and gD-1 of herpes simplex virus type 1 are involved in the "fusion from without" phenotype in different cell types.
1996
Previous studies have shown that certain strains of herpes simplex viruses type 1 (HSV-1) are able to induce “fusion from without” (FFWO) which means no transcription or translation of the viral genome happens. The main determinants for FFWO in BHK cells are mutations in the C-terminal part of gB-1. But single mutations in this part of the genome are not sufficient to transfer the FFWO phenotype also to Vero cells. Here, we report that FFWO of HSV strains indeed need additional mutations in the N-terminal part of gD in order to produce the FFWO phenotype in BHK and Vero cells. By marker transfer we are able to show that loss of mutations in the N-terminal part of gD influences the ability t…
Increased stability of the TM helix oligomer abrogates the apoptotic activity of the human Fas receptor
2021
Human death receptors control apoptotic events during cell differentiation, cell homeostasis and the elimination of damaged or infected cells. Receptor activation involves ligand-induced structural reorganizations of preformed receptor trimers. Here we show that the death receptor transmembrane domains only have a weak intrinsic tendency to homo-oligomerize within a membrane, and thus these domains potentially do not significantly contribute to receptor trimerization. However, mutation of Pro183 in the human CD95/Fas receptor transmembrane helix results in a dramatically increased interaction propensity, as shown by genetic assays. The increased interaction of the transmembrane domain is co…
Compartmentalization of Central Neurons inDrosophila: A New Strategy of Mosaic Analysis Reveals Localization of Presynaptic Sites to Specific Segment…
2002
Synaptogenesis in the CNS has received far less attention than the development of neuromuscular synapses, although only central synapses allow the study of neuronal postsynaptic mechanisms and display a greater variety of structural and functional features. This neglect is attributable mainly to the enormous complexity of the CNS, which makes the visualization of individual synapses on defined neuronal processes very difficult. We overcome this obstacle and demonstrate by confocal microscopy the specific arrangement of output synapses on individual neurites. These studies are performed via genetic mosaic strategies in the CNS of the fruitfly Drosophila melanogaster. First, we use targeted e…
Analysis of Drosophila salivary gland, epidermis and CNS development suggests an additional function of brinker in anterior-posterior cell fate speci…
2000
Salivary glands are simple structured organs which can serve as a model system in the study of organogenesis. Following a large EMS mutagenesis we have identified a number of genes required for normal salivary gland development. Mutations in the locus small salivary glands-1 (ssg-1) lead to a drastic reduction in the size of the salivary glands. The gene ssg-1 was cloned and subsequent sequence and genetic analysis showed identity to the recently published gene brinker. The salivary gland placode in brinker mutants appears reduced along both the anterior-posterior and dorso-ventral axis. Analysis of the brinker cuticle phenotype revealed a similar loss of anterior-posterior as well as later…
Mutations in spalt cause a severe but reversible neurodegenerative phenotype in the embryonic central nervous system ofDrosophila melanogaster
2002
The gene spalt is expressed in the embryonic central nervous system of Drosophila melanogaster but its function in this tissue is still unknown. To investigate this question, we used a combination of techniques to analyse spalt mutant embryos. Electron microscopy showed that in the absence of Spalt, the central nervous system cells are separated by enlarged extracellular spaces populated by membranous material at 60% of embryonic development. Surprisingly, the central nervous system from slightly older embryos (80% of development) exhibited almost wild-type morphology. An extensive survey by laser confocal microscopy revealed that thespalt mutant central nervous system has abnormal levels o…