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Mutant
About: Mutant is a research topic. Over the lifetime, 74520 publications have been published within this topic receiving 3477079 citations.
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TL;DR: The analysis of the GPR54 mutant mice revealed developmental abnormalities of both male and female genitalia and histopathological changes in tissues which normally contain sexually dimorphic features, suggesting a role for GPR 54/KiSS-1 in normal sexual development.
637 citations
TL;DR: MALT B cell lymphomas with t(1;14)(p22;q32) showed a recurrent breakpoint upstream of the promoter of a novel gene, Bcl10, a cellular homolog of the equine herpesvirus-2 E10 gene that contains an amino-terminal caspase recruitment domain (CARD) homologous to that found in several apoptotic molecules.
634 citations
TL;DR: It is shown that mice with a dominant mutation in Crygc gene that causes cataracts could be rescued by coinjection into zygotes of Cas9 mRNA and a single-guide RNA targeting the mutant allele, and were fertile and able to transmit the corrected allele to their progeny.
633 citations
01 Feb 2010
TL;DR: It is demonstrated that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation in multicellular organisms.
Abstract: The phenotypic differences between individual organisms can often be ascribed to underlying genetic and environmental variation. However, even genetically identical organisms in homogenous environments vary, suggesting that randomness in developmental processes such as gene expression may also generate diversity. In order to examine the consequences of gene expression variability in multicellular organisms, we studied intestinal specification in the roundworm Caenorhabditis elegans in which wild-type cell fate is invariant and controlled by a small transcriptional network. Mutations in elements of this network can have indeterminate effects: some mutant embryos fail to develop intestinal cells, while others produce intestinal precursors. By counting transcripts of the genes in this network in individual embryos, we show that the expression of an otherwise redundant gene becomes highly variable in the mutants and that this variation is thresholded to produce an ON/OFF expression pattern of the master regulatory gene of intestinal differentiation. Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation. In 1925, Timofeeff-Ressovsky and Romaschoff independently noticed that individuals harboring identical mutant alleles often exhibit either mutant or wild-type phenotypes, a property known as incomplete penetrance of the mutant phenotype1 – 5. Such variation can sometimes be traced to differences in genetic background or environmental conditions, but can also arise from random fluctuations in processes such as gene expression6. In clonal populations of microbes, these stochastic effects in gene expression can be used as a mechanism for generating phenotypic variation7 – 10, and multicellular organisms can also use variability to generate different cell types11 – 13. In general, though, the gene expression patterns of different cells during metazoan development must be coordinated to ensure proper tissue formation. This suggests that stochastic fluctuations in gene expression may be controlled or their effects may be buffered under normal conditions. Here, we examined the consequences of random variability in gene expression during intestinal specification by measuring expression in individual C. elegans embryos using a fluorescence in situ hybridization technique capable of detecting single mRNA molecules. We found that expression in the wild type network was highly regular, but that mutations to components of Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
632 citations
TL;DR: The results imply that the malignant phenotype of disease requires the combined activities of a H3K27 monomethylating enzyme (PRC2 containing WT EZH2 or EZh1) together with the mutant PRC2s for augmented conversion of H3k27 to the trimethylated form.
Abstract: EZH2, the catalytic subunit of the PRC2 complex, catalyzes the mono- through trimethylation of lysine 27 on histone H3 (H3K27). Histone H3K27 trimethylation is a mechanism for suppressing transcription of specific genes that are proximal to the site of histone modification. Point mutations of the EZH2 gene (Tyr641) have been reported to be linked to subsets of human B-cell lymphoma. The mutant allele is always found associated with a wild-type allele (heterozygous) in disease cells, and the mutations were reported to ablate the enzymatic activity of the PRC2 complex for methylating an unmodified peptide substrate. Here we demonstrate that the WT enzyme displays greatest catalytic efficiency (kcat/K) for the zero to monomethylation reaction of H3K27 and diminished efficiency for subsequent (mono- to di- and di- to trimethylation) reactions. In stark contrast, the disease-associated Y641 mutations display very limited ability to perform the first methylation reaction, but have enhanced catalytic efficiency for the subsequent reactions, relative to the WT enzyme. These results imply that the malignant phenotype of disease requires the combined activities of a H3K27 monomethylating enzyme (PRC2 containing WT EZH2 or EZH1) together with the mutant PRC2s for augmented conversion of H3K27 to the trimethylated form. To our knowledge, this is the first example of a human disease that is dependent on the coordinated activities of normal and disease-associated mutant enzymatic function.
632 citations