ENU Mutagenesis in the Mouse

Stottmann, Rolf; Beier, David R.

doi:10.1002/0471142905.hg1504s82

Cited by 15 publications

(8 citation statements)

References 42 publications

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“…In parallel, sperm and DNA from male progeny are banked for ‘genotype screens’, in which researchers assay the DNA (usually tens of thousands of samples from a single large ENU program) for point mutations in their gene of interest. The corresponding stored sperm samples are then used for in vitro fertilisation to (re)derive the relevant mouse line (Stottmann and Beier, 2014).…”

Section: Random Chemical Mutagenesismentioning

confidence: 99%

Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis

Giorgio

Maduro

Fisher

et al. 2019

Disease Models &Amp; Mechanisms

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A wide range of genetic mouse models is available to help researchers dissect human disease mechanisms. Each type of model has its own distinctive characteristics arising from the nature of the introduced mutation, as well as from the specific changes to the gene of interest. Here, we review the current range of mouse models with mutations in genes causative for the human neurodegenerative disease amyotrophic lateral sclerosis. We focus on the two main types of available mutants: transgenic mice and those that express mutant genes at physiological levels from gene targeting or from chemical mutagenesis. We compare the phenotypes for genes in which the two classes of model exist, to illustrate what they can teach us about different aspects of the disease, noting that informative models may not necessarily mimic the full trajectory of the human condition. Transgenic models can greatly overexpress mutant or wild-type proteins, giving us insight into protein deposition mechanisms, whereas models expressing mutant genes at physiological levels may develop slowly progressing phenotypes but illustrate early-stage disease processes. Although no mouse models fully recapitulate the human condition, almost all help researchers to understand normal and abnormal biological processes, providing that the individual characteristics of each model type, and how these may affect the interpretation of the data generated from each model, are considered and appreciated.

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Section: Random Chemical Mutagenesismentioning

confidence: 99%

Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis

Giorgio

Maduro

Fisher

et al. 2019

Disease Models &Amp; Mechanisms

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show abstract

“…Embryological development requires the cooperative patterning of cell types from multiple germ layers, which undergo complex morphogenetic movements to create the final body plan. We have been using a forward genetics approach to both identify novel regulators of embryonic organogenesis and to ascertain previously uncharacterized roles for known genes in these processes (Ha et al ., ; Herron et al ., ; Stottmann and Beier, , ). This has proven to be an efficient tool for gene and allele discovery.…”

Section: Introductionmentioning

confidence: 99%

Grhl2 is required in nonneural tissues for neural progenitor survival and forebrain development

Menke

Cionni

Siggers

et al. 2015

Genesis

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Grainyhead-like genes are part of a highly conserved gene family that play a number of roles in ectoderm development and maintenance in mammals. Here we identify a novel allele of Grhl2, cleft-face 3 (clft3), in a mouse line recovered from an ENU mutagenesis screen for organogenesis defects. Homozygous clft3 mutants have a number of phenotypes in common with other alleles of Grhl2. We note a significant effect of genetic background on the clft3 phenotype. One of these is a reduction in size of the telencephalon where we find abnormal patterns of neural progenitor mitosis and apoptosis in mutant brains. Interestingly, Grhl2 is not expressed in the developing forebrain, suggesting this is a survival factor for neural progenitors exerting a paracrine effect on the neural tissue from the overlying ectoderm where Grhl2 is highly expressed.

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“…N-ethyl-N-nitrosourea (ENU; Sigma-Aldrich, St. Louis, MO) was injected into pregnant mice on G13 to induce apoptosis in embryonic brains, as described previously. 14 Briefly, ENU was dissolved at 1% concentration in ethanol/phosphate/ citrate buffer 15 and injected intraperitoneally (IP) into pregnant mice at a dose of 25 mg/kg. Embryonic brains at E14 were fixed with a fixative as described below.…”

Section: Animal Treatmentmentioning

confidence: 99%

Improvement in Double Staining With Fluoro-Jade C and Fluorescent Immunostaining: FJC Staining Is Not Specific to Degenerating Mature Neurons

Ikenari

Kawaguchi

Ota

et al. 2021

J Histochem Cytochem.

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Fluoro-Jade C (FJC) staining has been used to detect degenerating neurons in tissue sections. It is a simple and easy staining procedure and does not depend on the manner of cell death. In some experiments, double staining with FJC and fluorescent immunostaining (FI) is required to identify cell types. However, pretreatment for FJC staining contains some processes that are harsh to fluorophores, and the FI signal is greatly reduced. To overcome this issue, we improved the double staining protocol to acquire clear double-stained images by introducing the labeled streptavidin–biotin system. In addition, several studies indicate that FJC can label non-degenerating glial cells, including resting/reactive astrocytes and activated microglia. Moreover, our previous study indicated that degenerating mesenchymal cells were also labeled by FJC, but it is still unclear whether FJC can label degenerating glial cells. Acute encephalopathy model mice contained damaged astrocytes with clasmatodendrosis, and 6-aminonicotinamide-injected mice contained necrotic astrocytes and oligodendrocytes. Using our improved double staining protocol with FJC and FI, we detected FJC-labeled degenerating astrocytes and oligodendrocytes with pyknotic nuclei. These results indicate that FJC is not specific to degenerating neurons in some experimental conditions:

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ENU Mutagenesis in the Mouse

Cited by 15 publications

References 42 publications

Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis

Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis

Grhl2 is required in nonneural tissues for neural progenitor survival and forebrain development

Improvement in Double Staining With Fluoro-Jade C and Fluorescent Immunostaining: FJC Staining Is Not Specific to Degenerating Mature Neurons

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