Genetic Mutants With Dysregulation of Corticotropin Pathways

2001 ◽  
pp. 143-173 ◽  
Author(s):  
Susan E. Murray ◽  
Sarah C. Coste ◽  
Iris Lindberg ◽  
Mary P. Stenzel-Poore
Keyword(s):  
Genetic Mutants

Inhibition of Xbra transcription activation causes defects in mesodermal patterning and reveals autoregulation of Xbra in dorsal mesoderm

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2427-2435 ◽  
Author(s):  
F.L. Conlon ◽  
S.G. Sedgwick ◽  
K.M. Weston ◽  
J.C. Smith
Keyword(s):  
Transcription Activation ◽  
Zebrafish Embryos ◽  
Transcription Activator ◽  
Activation Domain ◽  
Activation Domains ◽  
Dorsal Mesoderm ◽  
Transcription Activators ◽  
Carboxy Terminal ◽  
Genetic Mutants ◽  
Axial Development

The Brachyury (T) gene is required for formation of posterior mesoderm and for axial development in both mouse and zebrafish embryos. In this paper, we first show that the Xenopus homologue of Brachyury, Xbra, and the zebrafish homologue, no tail (ntl), both function as transcription activators. The activation domains of both proteins map to their carboxy terminal regions, and we note that the activation domain is absent in two zebrafish Brachyury mutations, suggesting that it is required for gene function. A dominant-interfering Xbra construct was generated by replacing the activation domain of Xbra with the repressor domain of the Drosophila engrailed protein. Microinjection of RNA encoding this fusion protein allowed us to generate Xenopus and zebrafish embryos which show striking similarities to genetic mutants in mouse and fish. These results indicate that the function of Brachyury during vertebrate gastrulation is to activate transcription of mesoderm-specific genes. Additional experiments show that Xbra transcription activation is required for regulation of Xbra itself in dorsal, but not ventral, mesoderm. The approach described in this paper, in which the DNA-binding domain of a transcription activator is fused to the engrailed repressor domain, should assist in the analysis of other Xenopus and zebrafish transcription factors.

scholarly journals Serine metabolism in the brain regulates starvation-induced sleep suppression in Drosophila melanogaster

2018 ◽  
Vol 115 (27) ◽  
pp. 7129-7134 ◽  
Author(s):  
Jun Young Sonn ◽  
Jongbin Lee ◽  
Min Kyung Sung ◽  
Hwajung Ri ◽  
Jung Kyoon Choi ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Hypomorphic Mutation ◽  
Cholinergic Signaling ◽  
Sleep Behaviors ◽  
Metabolizing Enzyme ◽  
Rate Limiting ◽  
The Brain ◽  
Serine Biosynthesis ◽  
Serine Metabolism ◽  
Genetic Mutants

Sleep and metabolism are physiologically and behaviorally intertwined; however, the molecular basis for their interaction remains poorly understood. Here, we identified a serine metabolic pathway as a key mediator for starvation-induced sleep suppression. Transcriptome analyses revealed that enzymes involved in serine biosynthesis were induced upon starvation in Drosophila melanogaster brains. Genetic mutants of astray (aay), a fly homolog of the rate-limiting phosphoserine phosphatase in serine biosynthesis, displayed reduced starvation-induced sleep suppression. In contrast, a hypomorphic mutation in a serine/threonine-metabolizing enzyme, serine/threonine dehydratase (stdh), exaggerated starvation-induced sleep suppression. Analyses of double mutants indicated that aay and stdh act on the same genetic pathway to titrate serine levels in the head as well as to adjust starvation-induced sleep behaviors. RNA interference-mediated depletion of aay expression in neurons, using cholinergic Gal4 drivers, phenocopied aay mutants, while a nicotinic acetylcholine receptor antagonist selectively rescued the exaggerated starvation-induced sleep suppression in stdh mutants. Taken together, these data demonstrate that neural serine metabolism controls sleep during starvation, possibly via cholinergic signaling. We propose that animals have evolved a sleep-regulatory mechanism that reprograms amino acid metabolism for adaptive sleep behaviors in response to metabolic needs.

scholarly journals Zebrafish: A Suitable Tool for the Study of Cell Signaling in Bone

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1911
Author(s):  
Maria Teresa Valenti ◽  
Giulia Marchetto ◽  
Monica Mottes ◽  
Luca Dalle Carbonare
Keyword(s):  
Osteogenesis Imperfecta ◽  
Signaling Pathways ◽  
Gaucher Disease ◽  
Model Organism ◽  
Bone Diseases ◽  
Zebrafish Model ◽  
Bone Differentiation ◽  
Transgenic Lines ◽  
Therapeutic Tools ◽  
Genetic Mutants

In recent decades, many studies using the zebrafish model organism have been performed. Zebrafish, providing genetic mutants and reporter transgenic lines, enable a great number of studies aiming at the investigation of signaling pathways involved in the osteoarticular system and at the identification of therapeutic tools for bone diseases. In this review, we will discuss studies which demonstrate that many signaling pathways are highly conserved between mammals and teleost and that genes involved in mammalian bone differentiation have orthologs in zebrafish. We will also discuss as human diseases, such as osteogenesis imperfecta, osteoarthritis, osteoporosis and Gaucher disease can be investigated in the zebrafish model.

Web application for genetic modification flux with database to estimate metabolic fluxes of genetic mutants

2016 ◽  
Vol 122 (1) ◽  
pp. 111-116
Author(s):  
Noorlin Mohd Ali ◽  
Ryo Tsuboi ◽  
Yuta Matsumoto ◽  
Daisuke Koishi ◽  
Kentaro Inoue ◽  
...  
Keyword(s):  
Genetic Modification ◽  
Web Application ◽  
Metabolic Fluxes ◽  
Genetic Mutants

scholarly journals Host-Microbe Interactions in Caenorhabditis elegans

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Rui Zhang ◽  
Aixin Hou
Keyword(s):  
Life Cycle ◽  
Microbial Pathogens ◽  
Model Organisms ◽  
Short Life ◽  
C Elegans ◽  
Complex Microbial Community ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Laboratory Maintenance ◽  
Genetic Mutants

A good understanding of how microbes interact with hosts has a direct bearing on our capability of fighting infectious microbial pathogens and making good use of beneficial ones. Among the model organisms used to study reciprocal actions among microbes and hosts, C. elegans may be the most advantageous in the context of its unique attributes such as the short life cycle, easiness of laboratory maintenance, and the availability of different genetic mutants. This review summarizes the recent advances in understanding host-microbe interactions in C. elegans. Although these investigations have greatly enhanced our understanding of C. elegans-microbe relationships, all but one of them involve only one or few microbial species. We argue here that more research is needed for exploring the evolution and establishment of a complex microbial community in the worm’s intestine and its interaction with the host.

Antheridiogen concentration and spore size predict gametophyte size in Ceratopteris richardii

Botany ◽  
2012 ◽  
Vol 90 (3) ◽  
pp. 175-179 ◽  
Author(s):  
Mike Ganger ◽  
Tiffany Sturey
Keyword(s):  
Sex Determination ◽  
Environmental Sex Determination ◽  
Wild Type ◽  
Ceratopteris Richardii ◽  
Spore Size ◽  
Male Development ◽  
Homosporous Fern ◽  
Type C ◽  
Slow Growing ◽  
Genetic Mutants

In many plants females invest more in reproduction than males. In organisms that exhibit environmental sex determination, individuals in low-quality environments or who are slow growing are expected to develop into males. The gametophytes of Ceratopteris richardii Brongn., a homosporous fern, may develop as males or hermaphrodites. Hermaphrodites secrete a pheromone called antheridiogen that induces undifferentiated spores to develop as males. Given that induction is not 100% in the presence of antheridiogen, it is hypothesized that resources may alter C. richardii gender decisions. An experiment was undertaken to determine (i) whether spore size predicts gender, (ii) whether spore size predicts gametophyte size, (iii) whether antheridiogen negatively affects the growth of C. richardii, and (iv) whether wild-type C. richardii and him1 mutants (genetic mutants disposed to male development regardless of antheridiogen presence) behave similarly in their response to antheridiogen. Spore size was not predictive of gender but was positively related to both male and hermaphrodite gametophyte size. Antheridiogen was found to slow the growth of male and hermaphrodite gametophytes of the wild type and male gametophytes of the him1 mutant. These results are supportive of the idea that gender may be determined indirectly through antheridiogen’s effect on gametophyte growth.

scholarly journals Baculovirus expression and potential diagnostic application of the gp51 envelope glycoprotein of genetic mutants of the bovine leukaemia virus

2019 ◽  
Vol 63 (1) ◽  
pp. 1-6
Author(s):  
Marzena Rola-Łuszczak ◽  
Agnieszka Grabowska ◽  
Bogusław Szewczyk ◽  
Jacek Kuźmak
Keyword(s):  
Envelope Glycoprotein ◽  
Insect Cells ◽  
3D Structure ◽  
Recombinant Baculovirus ◽  
Surface Glycoprotein ◽  
Serological Response ◽  
Bovine Leukaemia Virus ◽  
Leukaemia Virus ◽  
Baculovirus Expression ◽  
Genetic Mutants

AbstractIntroduction:Field isolates of bovine leukaemia virus (BLV) show the presence of a few amino acid substitutions in major conformational G and H epitopes on surface glycoprotein gp51. Potentially, these substitutions can affect the 3D structure of these epitopes leading to their diminished immunoreactivity. The aim of this study was to express three gp51 glycoproteins carrying mutated epitopes as recombinant baculovirus proteins in insect cells to test their immunoreactivity with bovine sera.Material and Methods:Envgene chimeras encoding mutated epitopes G and H in theenvbackbone of BLV FLK strain were constructed, cloned into pFastBac1 vector, and expressed in baculovirus.Results:The presence of recombinant gp51 protein in Sf9 insect cells was confirmed using monoclonal antibodies. ELISA tests were developed to check the immunoreactivity of recombinant protein with bovine sera.Conclusion:Recombinant gp51 proteins with altered G and H epitopes can be used for further studies to analyse the serological response of bovine sera towards BLV antigenic variants.

Isotopic tracing with carbon-13 in primary hepatocytes

2019 ◽  
Author(s):  
Katherine A Overmyer
Keyword(s):  
Culture Medium ◽  
Metabolic Flux ◽  
Isotopic Labeling ◽  
Flux Analysis ◽  
Isotopic Enrichment ◽  
Primary Hepatocytes ◽  
Expected Time ◽  
Isotopic Tracing ◽  
Intracellular Metabolism ◽  
Genetic Mutants

Abstract Isotopic labeling is commonly applied for investigating intracellular metabolism. The general workflow is to first introduce isotopically-labeled metabolites into the culture medium, then at defined time points wash and harvest cells, process samples for metabolomics analysis, and analyze the samples for isotopic enrichment in specified metabolite pools. Here we apply this technique to primary hepatocytes from mice. We introduce either 13C5 glutamine or 13C6 glucose at the typical media concentrations, 1:1 replacing the 12C version with 13C version. Cells are harvested at 0 and 30 min after isotope introduction, metabolites are extracted and then analyzed by GC-MS and LC-MS. The resulting data are used to compare relative 13C isotopic labeling in metabolites between different genetic mutants. This strategy is not suitable for directly quantifying metabolic flux (i.e., Metabolic flux analysis), but is useful for describing relative metabolic flux between two models. The expected time to complete is ~3-5 days.

scholarly journals Lack of Peroxisomal Catalase Causes a Progeric Phenotype inCaenorhabditis elegans

2004 ◽  
Vol 279 (19) ◽  
pp. 19996-20001 ◽  
Author(s):  
Oleh I. Petriv ◽  
Richard A. Rachubinski
Keyword(s):  
Life Span ◽  
Aging Process ◽  
Target Genes ◽  
Egg Laying ◽  
C Elegans ◽  
Extend Life Span ◽  
Genes Encoding ◽  
Shorten Life Span ◽  
Development And Aging ◽  
Genetic Mutants

Studies using the nematodeCaenorhabditis elegansas a model system to investigate the aging process have implicated the insulin/insulin-like growth factor-I signaling pathway in the regulation of organismal longevity through its action on a subset of target genes. These targets can be classified into genes that shorten or extend life-span upon their induction. Genes that shorten life-span include a variety of stress response genes, among them genes encoding catalases; however, no evidence directly implicates catalases in the aging process of nematodes or other organisms. Using genetic mutants, we show that lack of peroxisomal catalase CTL-2 causes a progeric phenotype inC. elegans. Lack of peroxisomal catalase also affects the developmental program ofC. elegans, since Δctl-2mutants exhibit decreased egg laying capacity. In contrast, lack of cytosolic catalase CTL-1 has no effect on either nematode aging or egg laying capacity. The Δctl-2mutation also shortens the maximum life-span of the long lived Δclk-1mutant and accelerates the onset of its egg laying period. The more rapid aging of Δctl-2worms is apparently not due to increased carbonylation of the majorC. elegansproteins, although altered peroxisome morphology in the Δctl-2mutant suggests that changes in peroxisomal function, including increased production of reactive oxygen species, underlie the progeric phenotype of the Δctl-2mutant. Our findings support an important role for peroxisomal catalase in both the development and aging ofC. elegansand suggest the utility of the Δctl-2mutant as a convenient model for the study of aging and the human diseases acatalasemia and hypocatalasemia.

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