A5087224081- Amyotrophic Lateral Sclerosis Research
- Genetics and Neurodevelopmental Disorders
- Bacterial Genetics and Biotechnology
- Neuroscience and Neuropharmacology Research
- Bacteriophages and microbial interactions
- T-cell and B-cell Immunology
- Ion channel regulation and function
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Regulation of Appetite and Obesity
- Neurogenetic and Muscular Disorders Research
- Immunotherapy and Immune Responses
- Ginger and Zingiberaceae research
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- Endoplasmic Reticulum Stress and Disease
- Genetic Mapping and Diversity in Plants and Animals
- Natural Antidiabetic Agents Studies
- Genetic Neurodegenerative Diseases
- Animal Genetics and Reproduction
- Plant Molecular Biology Research
- Diet, Metabolism, and Disease
Jackson Laboratory
1999-2025
Pennington Biomedical Research Center
2002-2014
Louisiana State University System
2008-2014
Louisiana State University Agricultural Center
2008
Rutgers, The State University of New Jersey
2008
University of Arkansas at Fayetteville
2008
Louisiana State University
1999-2004
Medical Research Council
1998
The University of Texas Southwestern Medical Center
1997
University of Illinois Urbana-Champaign
1990-1993
Abstract This paper presents the eleventh update of human obesity gene map, which incorporates published results up to end October 2004. Evidence from single‐gene mutation cases, Mendelian disorders exhibiting as a clinical feature, transgenic and knockout murine models relevant obesity, quantitative trait loci (QTLs) animal cross‐breeding experiments, association studies with candidate genes, linkages genome scans is reviewed. As 2004, 173 cases due mutations in 10 different genes have been...
Loss of nuclear TDP-43 is a hallmark neurodegeneration in proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). mislocalization results cryptic splicing polyadenylation pre-messenger RNAs (pre-mRNAs) encoding stathmin-2 (also known as SCG10), protein that required for axonal regeneration. We found binding to GU-rich region sterically blocked recognition the 3' splice site
Insulin receptor substrate (IRS) has been suggested as a molecular target of free fatty acids (FFAs) for insulin resistance. However, the signaling pathways by which FFAs lead to inhibition IRS function remain be established. In this study, we explored FFA-signaling pathway that contributes serine phosphorylation and degradation IRS-1 in adipocytes dietary obese mice. Linoleic acid, an FFA used resulted reduction insulin-induced glucose uptake 3T3-L1 adipocytes. This mimics resistance...
The hypoglycemic effects of high dose salicylates in the treatment diabetes were documented before advent insulin. However, molecular mechanisms by which exert these anti-diabetic are not well understood. In this study, we analyzed aspirin (acetylsalicylic acid) on serine phosphorylation insulin receptor substrate 1 (IRS-1) cells treated with tumor necrosis factor (TNF)-α. Phosphorylation IRS-1 at Ser307, Ser267, and Ser612 was monitored immunoblotting phospho-specific antibodies. 3T3-L1 Hep...
Minor histocompatibility (H) Ags elicit T cell responses and thereby cause chronic graft rejection graft-vs-host disease among MHC identical individuals. Although numerous independent H loci exist in mice of a given haplotype, certain dominate the immune response are thus considerable conceptual therapeutic importance. To identify these their genes, lacZ-inducible CD8+ hybrids were generated by immunizing C57BL/6 (B6) with BALB.B spleen cells. The cDNA clones encoding precursor for antigenic...
Blood-CNS barrier disruption is a hallmark of numerous neurological disorders, yet whether breakdown sufficient to trigger neurodegenerative disease remains unresolved. Therapeutic strategies mitigate hyperpermeability are also limited. Dominant missense mutations the cation channel transient receptor potential vanilloid 4 (TRPV4) cause forms hereditary motor neuron disease. To gain insights into cellular basis these we generated knock-in mouse models TRPV4 channelopathy by introducing two...
KCNQ2 variants in children with neurodevelopmental impairment are difficult to assess due their heterogeneity and unclear pathogenic mechanisms. We describe a child neonatal-onset epilepsy, developmental of intermediate severity, G256W heterozygosity. Analyzing prior channel cryoelectron microscopy models revealed G256 as node an arch-shaped non-covalent bond network linking S5, the pore turret, ion path. Co-expression dominantly suppressed conduction by wild-type subunits heterologous...
Mutations in coiled-coil-helix-coiled-coil-helix-domain containing 10 (CHCHD10), a mitochondrial twin CX9C protein whose function is still unknown, cause myopathy, motor neuron disease, frontotemporal dementia, and Parkinson's disease. Here, we investigate CHCHD10 topology its interactome, as well the effects of depletion or expression disease-associated mutations wild-type cells. We find that associates with membranes intermembrane space, where it interacts closely related protein, CHCHD2....
Abstract Genetic variants that define two distinct haplotypes at the TMEM106B locus have been implicated in multiple neurodegenerative diseases and healthy brain ageing. In frontotemporal dementia (FTD), high expressing risk haplotype was shown to increase susceptibility for FTD with TDP-43 inclusions (FTD-TDP) modify disease penetrance progranulin mutation carriers (FTD-GRN). To elucidate biological function of determine whether lowering may be a viable therapeutic strategy, we performed...
Drugs that improve chronic hyperglycemia independently of insulin signaling or reduction adiposity dietary fat intake may be highly desirable. Ad36, a human adenovirus, promotes glucose uptake in vitro proximal signaling. We tested the ability Ad36 to glycemic control vivo and determined if natural infection humans is associated with better control. C57BL/6J mice fed chow diet made diabetic high-fat (HF) were mock infected adenovirus Ad2 as for infection. Postinfection (pi), systemic...
The use of mouse models in biomedical research and preclinical drug evaluation is on the rise. advent new molecular genome-altering technologies such as CRISPR/Cas9 allows for genetic mutations to be introduced into germ line a faster less expensively than previous methods. In addition, rapid progress development somatic transgenesis using viral vectors, well manipulations gene expression with siRNAs antisense oligonucleotides, allow even greater exploration genomics systems biology. These...
During endoplasmic reticulum-associated degradation (ERAD), the cytoplasmic enzyme N-glycanase 1 (NGLY1) is proposed to remove N-glycans from misfolded N-glycoproteins after their retrotranslocation ER cytosol. We previously reported that NGLY1 regulates Drosophila BMP signaling in a tissue-specific manner (Galeone et al., 2017). Here, we establish Dpp and its mouse ortholog BMP4 as biologically relevant targets of find, unexpectedly, NGLY1-mediated deglycosylation required for...
N-Glycanase 1 (NGLY1) is a cytoplasmic deglycosylating enzyme. Loss-of-function mutations in the NGLY1 gene cause deficiency, which characterized by developmental delay, seizures, and lack of sweat tears. To model phenotypic variability observed among patients, we crossed Drosophila deficiency onto panel genetically diverse strains. The resulting progeny showed spectrum from 0 to 100% lethality. Association analysis on lethality phenotype, as well an evolutionary rate covariation analysis,...
Quantitative trait locus (QTL) analysis of genetic crosses has proven to be a useful tool for identifying loci associated with specific phenotypes and dissecting components complex traits.Inclusion mutation that interacts epistatically QTLs in is unique potentially powerful method revealing the function novel genes pathways. Although we know within tubgene leads obesity cochlear retinal degeneration, biological gene mechanism by which it induces its are not known. In current study, QTL...
The present study investigated the inheritance of dietary fat, carbohydrate, and kilocalorie intake traits in an F 2 population derived from intercross between C57BL/6J (fat-preferring) CAST/EiJ (carbohydrate-preferring) mice. Mice were phenotyped for self-selected food a paradigm which provided 10 days choice two macronutrient diets containing 78/22% energy as composite either fat/protein or carbohydrate/protein. Quantitative trait locus (QTL) analysis identified six significant loci...