To study the profile and regulation of apolipoprotein E (apoE) expression in CNS, we generated mice which apoE can be detected vivo with unprecedented sensitivity resolution. cDNA encoding enhanced green fluorescent protein (EGFP) a stop codon was inserted by gene targeting into locus (EGFP ) immediately after translation initiation site. Insertion EGFP one allele provides real-time location marker ; remaining is sufficient to maintain normal cellular physiology. In heterozygous mice, highly...

Apolipoprotein E4 (apoE4) plays a major role in the pathogenesis of Alzheimer's disease. Brain amyloid-β (Aβ) accumulation depends on age and apoE isoforms (apoE4 > apoE3) both humans transgenic mouse models. levels are also isoform dependent, but opposite direction < apoE3). Thus, one prevailing hypothesis is to increase brain expression reduce Aβ levels. To test this hypothesis, we generated mutant human amyloid precursor protein mice expressing or two copies APOE3 APOE4 gene that...

Both cDNA and genomic clones encoding human apolipoprotein (apo-) A-IV have been isolated characterized.Southern blot analyses of apo-A-IV genecontaining cosmids revealed that the gene is linked to apo-'A-I apo-C-I11 genes within a 20kilobase span chromosome 11 DNA.The located about 14 kilobases downstream from apo-A-I in same orientation, with between them opposite orientation.The nucleotide sequence corresponding mRNA was determined, derived amino acid showed mature plasma contained 376...

Apolipoprotein E4 (apoE4), the major genetic risk factor for late onset Alzheimer disease, assumes a pathological conformation, intramolecular domain interaction. ApoE4 interaction mediates detrimental effects of apoE4, including decreased mitochondrial cytochrome c oxidase subunit 1 levels, reduced motility, and neurite outgrowth in vitro. Mutant apoE4 (apoE4-R61T) lacks interaction, behaves like apoE3, does not cause effects. To identify small molecules that inhibit (i.e. structure...

Tauopathies represent a group of neurodegenerative disorders characterized by the accumulation pathological TAU protein in brains. We report human neuronal model tauopathy derived from induced pluripotent stem cells (iPSCs) carrying TAU-A152T mutation. Using zinc-finger nuclease-mediated gene editing, we generated two isogenic iPSC lines: one with mutation corrected, and another homozygous engineered. The A152T increased fragmentation phosphorylation, leading to neurodegeneration especially...

The glycosylation of human apolipoprotein (apo) E was examined with purified plasma apoE and produced by transfected cell lines. carbohydrate attachment site localized to a single tryptic peptide (residues 192–206). Sequence analysis amino sugar this derived from asialo-, monosialo-, or disialo-apoE indicated that the moiety is attached only Thr194 in monosialo- asialo-apoE not glycosylated. Mammalian cells normally do express were plasmid expression vectors test utilization potential sites...

The gene for human apolipoprotein (apo) C-I was selected from genomic cosmid and lambda libraries. Restriction endonuclease analysis showed that the apoC-I is located 5.5 kilobases downstream of apoE. A copy gene, apoC-I', 7.5 gene. Both genes contain four exons three introns; 4653 base pairs long, apoC-I' 4387 pairs. In each first intron 20 nucleotides upstream translation start signal; second intron, within codon Gly-7 signal peptide region; third Arg39 mature plasma protein coding region....

Neuronal expression of apolipoprotein (apo) E4 may contribute to the pathogenesis Alzheimer's disease (AD). In studying how apoE is regulated in neurons, we identified a splicing variant mRNA with intron-3 retention (apoE-I3). ApoE-I3 was detected neuronal cell lines and primary but not astrocytic or astrocytes, from humans mice by reverse transcription (RT)-PCR. both wild-type human knock-in mice, apoE-I3 found predominantly cortical hippocampal neurons situ hybridization. Cell...

Apolipoprotein D (ApoD) expression increases in several neurological disorders and spinal cord injury. We provide a report of physiological role for human ApoD (hApoD): Flies overexpressing hApoD are long-lived protected against stress conditions associated with aging neurodegeneration, including hyperoxia, dietary paraquat, heat stress. show that the fly ortholog, Glial Lazarillo, is strongly up-regulated response to these extrinsic stresses also can protect vitro-cultured cells situations...

Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD). ApoE4 has sex-dependent effects, whereby of developing AD higher in apoE4-expressing females than males. However, mechanism underlying sex difference, relation to apoE4, unknown. Previous findings indicate that apoE4 causes age-dependent impairments hilar GABAergic interneurons female mice, leading learning and memory deficits. Here, we investigate whether detrimental effects on are using apoE knock-in...

Apolipoprotein (apo) E4 is expressed in many types of brain cells, associated with age-dependent decline learning and memory humans, the major genetic risk factor for AD. To determine whether detrimental effects apoE4 depend on its cellular sources, we generated human apoE knock-in mouse models which APOE gene conditionally deleted astrocytes, neurons, or GABAergic interneurons. Here report that deletion astrocytes does not protect aged mice from apoE4-induced interneuron loss deficits. In...

The specificity of expression in the liver human apolipoprotein (apo) E/C-I gene locus is determined by a hepatic control region (HCR) that located 15 kilobases downstream apoE gene. DNase I footprint studies this sequence using nuclear extracts identified HCR enriched protein-binding sites. Nuclease analysis chromatin revealed liver-specific I-hypersensitive sites were associated with region, and additional nuclease-sensitive identified. domain has limited binding affinity for scaffold....

We have identified a second hepatic control region (HCR-2) in the human apolipoprotein (apo) E gene locus that confers liver expression of apoE transgenic mice. This HCR-2 sequence is located 27 kilobases downstream and 10 previously described liver-specific enhancer (HCR-1). Nucleotide analysis revealed shares 85% identity to functional 319-base pair domain HCR-1. To test its activity, mice were prepared with fusion construct containing fragment, which not normally expressed liver, ligated...

An enhancer element in the 5' flanking region of human apolipoprotein E gene, known as upstream regulatory 1 (URE1), has previously been implicated expression this gene. The URE1 element, which spans nucleotides -193 to -124 5'-flanking contains two sequences that bind nuclear proteins, determined by DNase I footprinting assay. In present study URE1, we have characterized these further. Deletion one footprint sequences, at -161 -141, reduced activity substantially. A 30-base pair...

The ability to distinguish between similar experiences is a critical feature of episodic memory and primarily regulated by the dentate gyrus (DG) region hippocampus. However, molecular mechanisms underlying such pattern separation tasks are poorly understood. We report novel role for small GTPase ADP ribosylation factor 4 (Arf4) in controlling regulating dendritic spine development. Arf4+/− mice at 4–5 months age display severe impairments task, as well significant loss smaller miniature...

Placental progesterone synthesis exposes the fetus to high levels of and metabolites during late gestation which may influence fetal behaviour. To determine role maternal in control arousal state breathing movements (FBM), effect raising lowering concentrations was examined chronically catheterised sheep. Fetal vascular catheters, tracheal amniotic fluid catheters as well electrodes for recording electrocortical (ECoG), electro-ocular (EOG) nuchal muscle electromyographic (EMG) activity were...

The expression of the apolipoprotein (apo) E and C-l genes in different tissues is determined by distinct regulatory elements that are distributed upstream downstream these genes, including a common hepatic control region located 18 kb apoE gene promoter. contains all sequences needed to direct liver, but it requires presence non-specific element proximal promoter for its action.

Journal Article Evaluation of Off-Odor in Malathion-Treated Wheat Get access David W. Walker, Walker Search for other works by this author on: Oxford Academic PubMed Google Scholar Ruth Locke Economic Entomology, Volume 52, Issue 5, 1 October 1959, Page 1013, https://doi.org/10.1093/jee/52.5.1013 Published: 01 1959 history Accepted: 17 May

The structures of the major human apolipoprotein genes have been determined. for apoE, apoC–I, apoC–II, apoC–III, apoA–I, apoA–II and apoA–IV similar structures, consisting four exons three introns, which suggests that they evolved from a common ancestral gene. third fourth gene appear to duplication 66-nucleotide repeat unit encodes 22-residue α-helical peptide element amphipathic character. apoC–III are linked closely within 20-kilobase (kb) span chromosome 11. apoE apoC–I genes, together...

Human Menkes disease is a lethal neurodegenerative disorder of copper metabolism that caused by mutations in the ATP7A copper-transporting gene. In present study, we attempted to construct Drosophila model RNA interference (RNAi)-induced silencing DmATP7 , orthologue mammalian digestive tract. Here, show lowered level mRNA tract results reduced content head and rest body surviving adults, presumably owing entrapment gut. Similar patients, majority flies exhibit an impaired neurological...

Tau is a microtubule-binding protein in neurons, and its pathological accumulation causes tauopathies, including Alzheimer's disease (AD) frontotemporal dementia (FTD). Removing tau from mice prevents genetic chemically induced seizures the detrimental effects of amyloid-beta (Aβ) peptides, major pathogenic factor AD. While lowering may be an effective therapeutic approach to treating AD, FTD, seizures, other neurological diseases, safety efficacy this human neurons are unknown. Thus, before...