THE NEED TO DETECT CHEMICALLY INDUCED MUTATIONS IN EXPERIMENTAL ANIMALS

1972 ◽  
pp. 67-79 ◽  
Author(s):  
Marvin S. Legator
Keyword(s):  
Induced Mutations ◽  
Experimental Animals ◽  
Chemically Induced

scholarly journals Construction and Characterization of Mutations within theKlebsiella mrkD1P Gene That Affect Binding to Collagen Type V

1999 ◽  
Vol 67 (4) ◽  
pp. 1672-1676 ◽  
Author(s):  
Tricia A. Sebghati ◽  
Steven Clegg
Keyword(s):  
Collagen Type ◽  
Gene Products ◽  
Induced Mutations ◽  
Binding Properties ◽  
Collagen Binding ◽  
Chemically Induced ◽  
Collagen Type V ◽  
Type V ◽  
Type 3

ABSTRACT The fimbria-associated MrkD1P protein mediates adherence of type 3 fimbriate strains of Klebsiella pneumoniae to collagen type V. Currently, three different MrkD adhesins have been described in Klebsiella species, and each possesses a distinctive binding pattern. Therefore, the binding abilities of mutants possessing defined mutations within themrkD 1P gene were examined in order to determine whether specific regions of the adhesin molecule were responsible for collagen binding. Both site-directed and chemically induced mutations were constructed within mrkD 1P, and the ability of the gene products to be incorporated into fimbrial appendages or bind to collagen was determined. Binding to type V collagen was not associated solely with one particular region of the MrkD1Pprotein, and two classes of nonadhesive mutants were isolated. In one class of mutants, the MrkD adhesin was not assembled into the fimbrial shaft, whereas in the second class of mutants, the adhesin was associated with fimbriae but did not bind to collagen. Both hemagglutinating and collagen-binding activities were associated with the MrkD1P molecule, since P pili and type 3 fimbriae carrying adhesive MrkD proteins exhibited identical binding properties.

scholarly journals Chemically induced mutations in a MutaMouse reporter gene inform mechanisms underlying human cancer mutational signatures

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Marc A. Beal ◽  
Matthew J. Meier ◽  
Danielle P. LeBlanc ◽  
Clotilde Maurice ◽  
Jason M. O’Brien ◽  
...  
Keyword(s):  
Human Cancer ◽  
Published Data ◽  
Induced Mutations ◽  
Lung Cancers ◽  
Human Cancers ◽  
Chemically Induced ◽  
Mutation Pattern ◽  
Environmental Causes ◽  
Next Generation Sequencing Ngs

AbstractTransgenic rodent (TGR) models use bacterial reporter genes to quantify in vivo mutagenesis. Pairing TGR assays with next-generation sequencing (NGS) enables comprehensive mutation pattern analysis to inform mutational mechanisms. We used this approach to identify 2751 independent lacZ mutations in the bone marrow of MutaMouse animals exposed to four chemical mutagens: benzo[a]pyrene, N-ethyl-N-nitrosourea, procarbazine, and triethylenemelamine. We also collected published data for 706 lacZ mutations from eight additional environmental mutagens. We report that lacZ gene sequencing generates chemical-specific mutation signatures observed in human cancers with established environmental causes. For example, the mutation signature of benzo[a]pyrene, a carcinogen present in tobacco smoke, matched the signature associated with tobacco-induced lung cancers. Our results suggest that the analysis of chemically induced mutations in the lacZ gene shortly after exposure provides an effective approach to characterize human-relevant mechanisms of carcinogenesis and propose novel environmental causes of mutation signatures observed in human cancers.

scholarly journals Whole genome profiling of spontaneous and chemically induced mutations in Toxoplasma gondii

BMC Genomics ◽  
2014 ◽  
Vol 15 (1) ◽  
pp. 354 ◽  
Author(s):  
Andrew Farrell ◽  
Bradley I Coleman ◽  
Brian Benenati ◽  
Kevin M Brown ◽  
Ira J Blader ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Whole Genome ◽  
Induced Mutations ◽  
Genome Profiling ◽  
Chemically Induced ◽  
Whole Genome Profiling

scholarly journals Enhanced susceptibility to chemically induced colitis caused by excessive endosomal TLR signaling in LRBA-deficient mice

2019 ◽  
Vol 116 (23) ◽  
pp. 11380-11389 ◽  
Author(s):  
Kuan-wen Wang ◽  
Xiaoming Zhan ◽  
William McAlpine ◽  
Zhao Zhang ◽  
Jin Huk Choi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Type I ◽  
Induced Mutations ◽  
Tlr Signaling ◽  
Nonsense Mutations ◽  
Chemically Induced ◽  
Inflammatory Bowel ◽  
Deficient Mice ◽  
Stimulation Of

LPS-responsive beige-like anchor (LRBA) protein deficiency in humans causes immune dysregulation resulting in autoimmunity, inflammatory bowel disease (IBD), hypogammaglobulinemia, regulatory T (Treg) cell defects, and B cell functional defects, but the cellular and molecular mechanisms responsible are incompletely understood. In an ongoing forward genetic screen forN-ethyl-N-nitrosourea (ENU)-induced mutations that increase susceptibility to dextran sodium sulfate (DSS)-induced colitis in mice, we identified two nonsense mutations inLrba. Although Tregcells have been a main focus in LRBA research to date, we found that dendritic cells (DCs) contribute significantly to DSS-induced intestinal inflammation in LRBA-deficient mice.Lrba−/−DCs exhibited excessive IRF3/7- and PI3K/mTORC1-dependent signaling and type I IFN production in response to the stimulation of the Toll-like receptors (TLRs) 3, TLR7, and TLR9. Substantial reductions in cytokine expression and sensitivity to DSS in LRBA-deficient mice were caused by knockout ofUnc93b1, a chaperone necessary for trafficking of TLR3, TLR7, and TLR9 to endosomes. Our data support a function for LRBA in limiting endosomal TLR signaling and consequent intestinal inflammation.

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