scholarly journals Novel dominant-negative mutation within the six domain of the conserved eye specification genesine oculis inhibits eye development inDrosophila

2005 ◽  
Vol 232 (3) ◽  
pp. 753-766 ◽  
Author(s):  
Kristin Roederer ◽  
Loralyn Cozy ◽  
Jason Anderson ◽  
Justin P. Kumar
Keyword(s):  
Eye Development ◽  
Dominant Negative ◽  
Dominant Negative Mutation

scholarly journals The Role of Alcohol, LPS Toxicity, and ALDH2 in Dental Bony Defects

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 651
Author(s):  
Hsiao-Cheng Tsai ◽  
Che-Hong Chen ◽  
Daria Mochly-Rosen ◽  
Yi-Chen Ethan Li ◽  
Min-Huey Chen
Keyword(s):  
Bone Loss ◽  
Bacterial Infection ◽  
Bone Regeneration ◽  
Alcohol Drinking ◽  
Bacterial Species ◽  
Dominant Negative ◽  
Enzyme Inactivation ◽  
Wild Type ◽  
Micro Computed Tomography ◽  
Dominant Negative Mutation

It is estimated that 560 million people carry an East Asian-specific ALDH2*2 dominant-negative mutation which leads to enzyme inactivation. This common ALDH2 polymorphism has a significant association with osteoporosis. We hypothesized that the ALDH2*2 mutation in conjunction with periodontal Porphyromonas gingivalis bacterial infection and alcohol drinking had an inhibitory effect on osteoblasts and bone regeneration. We examined the prospective association of ALDH2 activity with the proliferation and mineralization potential of human osteoblasts in vitro. The ALDH2 knockdown experiments showed that the ALDH2 knockdown osteoblasts lost their proliferation and mineralization capability. To mimic dental bacterial infection, we compared the dental bony defects in wild-type mice and ALDH2*2 knockin mice after injection with purified lipopolysaccharides (LPS), derived from P. gingivalis which is a bacterial species known to cause periodontitis. Micro-computed tomography (micro-CT) scan results indicated that bone regeneration was significantly affected in the ALDH2*2 knockin mice with about 20% more dental bony defects after LPS injection than the wild-type mice. Moreover, the ALDH2*2 knockin mutant mice had decreased osteoblast growth and more dental bone loss in the upper left jaw region after LPS injection. In conclusion, these results indicated that the ALDH2*2 mutation with alcohol drinking and chronic exposure to dental bacterial-derived toxin increased the risk of dental bone loss.

scholarly journals Cellular Werner Phenotypes in Mice Expressing a Putative Dominant-Negative Human WRN Gene

Genetics ◽  
2000 ◽  
Vol 154 (1) ◽  
pp. 357-362
Author(s):  
Lan Wang ◽  
Charles E Ogburn ◽  
Carol B Ware ◽  
Warren C Ladiges ◽  
Hagop Youssoufian ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mice ◽  
Werner Syndrome ◽  
Dominant Negative ◽  
Dominant Negative Mutation ◽  
Fibroblast Cultures ◽  
Age Related

Abstract Mutations at the Werner helicase locus (WRN) are responsible for the Werner syndrome (WS). WS patients prematurely develop an aged appearance and various age-related disorders. We have generated transgenic mice expressing human WRN with a putative dominant-negative mutation (K577M-WRN). Primary tail fibroblast cultures from K577M-WRN mice showed three characteristics of WS cells: hypersensitivity to 4-nitroquinoline-1-oxide (4NQO), reduced replicative potential, and reduced expression of the endogenous WRN protein. These data suggest that K577M-WRN mice may provide a novel mouse model for the WS.

scholarly journals The new kid on the block: A dominant‐negative mutation of phototropin1 enhances carotenoid content in tomato fruits

2021 ◽  
Author(s):  
Himabindu Vasuki Kilambi ◽  
Alekhya Dindu ◽  
Kapil Sharma ◽  
Narasimha Rao Nizampatnam ◽  
Neha Gupta ◽  
...  
Keyword(s):  
Dominant Negative ◽  
Carotenoid Content ◽  
Tomato Fruits ◽  
Dominant Negative Mutation

P273 A case of agammaglobulinemia attributed to heterozygous, dominant-negative mutation in transcription factor E47

2017 ◽  
Vol 119 (5) ◽  
pp. S69
Author(s):  
E. Feuille ◽  
B. Boisson ◽  
Y. Itan ◽  
J. Casanova ◽  
C. Cunningham-Rundles
Keyword(s):  
Transcription Factor ◽  
Dominant Negative ◽  
Dominant Negative Mutation

scholarly journals Suppressor Mutations Bypass the Requirement of fluG for Asexual Sporulation and Sterigmatocystin Production in Aspergillus nidulans

Genetics ◽  
2003 ◽  
Vol 165 (3) ◽  
pp. 1083-1093
Author(s):  
Jeong-Ah Seo ◽  
Yajun Guan ◽  
Jae-Hyuk Yu
Keyword(s):  
Aspergillus Nidulans ◽  
Molecular Mechanisms ◽  
Dominant Negative ◽  
Wild Type ◽  
Dominant Mutation ◽  
Site Mutation ◽  
Asexual Sporulation ◽  
Dominant Negative Mutation ◽  
Suppressor Mutations ◽  
Early Developmental

Abstract Asexual sporulation (conidiation) in the filamentous fungus Aspergillus nidulans requires the early developmental activator fluG. Loss of fluG results in the blockage of both conidiation and production of the mycotoxin sterigmatocystin (ST). To investigate molecular mechanisms of fluG-dependent developmental activation, 40 suppressors of fluG (SFGs) that conidiate without fluG have been isolated and characterized. Genetic analyses showed that an individual suppression is caused by a single second-site mutation, and that all sfg mutations but one are recessive. Pairwise meiotic crosses grouped mutations to four loci, 31 of them to sfgA, 6 of them to sfgB, and 1 each to sfgC and sfgD, respectively. The only dominant mutation, sfgA38, also mapped to the sfgA locus, suggesting a dominant negative mutation. Thirteen sfgA and 1 sfgC mutants elaborated conidiophores in liquid submerged culture, indicating that loss of either of these gene functions not only bypasses fluG function but also results in hyperactive conidiation. While sfg mutants show varying levels of restored conidiation, all recovered the ability to produce ST at near wild-type levels. The fact that at least four loci are defined by recessive sfg mutations indicates that multiple genes negatively regulate conidiation downstream of fluG and that the activity of fluG is required to remove such repressive effects.

Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells in response to heat shock

2001 ◽  
Vol 114 (6) ◽  
pp. 1145-1153 ◽  
Author(s):  
C. Gao ◽  
S. Negash ◽  
H.S. Wang ◽  
D. Ledee ◽  
H. Guo ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cell Line ◽  
Fluorescent Protein ◽  
Morphological Changes ◽  
Normal Growth ◽  
Dominant Negative ◽  
Specific Expression ◽  
Cell Matrix ◽  
Dominant Negative Mutation ◽  
U373 Cells

The cyclin-dependent kinase member, Cdk5, is expressed in a variety of cell types, but neuron-specific expression of its activator, p35, is thought to limit its activity to neurons. Here we demonstrate that both Cdk5 and p35 are expressed in the human astrocytoma cell line, U373. Cdk5 and p35 are present in the detergent-insoluble cytoskeletal fraction of this cell line and Cdk5 localizes to filopodia and vinculin-rich regions of cell-matrix contact in lamellopodia. When exposed to a 46(o)C heat shock, U373 cells change shape, lose cell-matrix contacts and show increased levels of apoptosis. To test whether Cdk5 activation might play a role in these events, U373 cells were stably transfected with histidine-tagged or green fluorescent protein-tagged constructs of Cdk5 or a dominant negative mutation, Cdk5T33. Under normal growth conditions, growth characteristics of the stably transfected lines were indistinguishable from untransfected U373 cells and Cdk5 localization was not changed. However, when subjected to heat shock, cells stably transfected with Cdk5-T33 remained flattened, showed little loss of cell-matrix adhesion, and exhibited significantly lower levels of apoptosis. In contrast, cells that overexpressed wild-type Cdk5 showed morphological changes similar to those seen in untransfected U373 cells in response to heat shock and had significantly higher levels of apoptosis. Heat-shocked cells showed changes in p35 mobility and stability of the Cdk5/p35 complex consistent with endogenous Cdk5 activity. Together these findings suggest that endogenous Cdk5 activity may play a key role in regulating morphology, attachment, and apoptosis in U373 cells, and raise the possibility that Cdk5 may be a general regulator of cytoskeletal organization and cell adhesion in both neuronal and non-neuronal cells.

scholarly journals Differential Recruitment of Nuclear Coregulators Directs the Isoform-Dependent Action of Mutant Thyroid Hormone Receptors

2011 ◽  
Vol 25 (6) ◽  
pp. 908-921 ◽  
Author(s):  
Laura Fozzatti ◽  
Changxue Lu ◽  
Dong-Wook Kim ◽  
Sheue-yann Cheng
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptors ◽  
Biological Activities ◽  
Liver Lipid ◽  
Dominant Negative ◽  
Mutant Mice ◽  
Regulatory Proteins ◽  
Thyroid Hormone Receptors ◽  
Dominant Negative Mutation

Abstract Studies using mice deficient in thyroid hormone receptors (TR) indicate that the two TR isoforms, TRα1 and TRβ1, in addition to mediating overlapping biological activities of the thyroid hormone, T3, also mediate distinct functions. Mice harboring an identical dominant negative mutation (denoted PV) at the C terminus of TRα1 (Thra1PV mice) or β1 (ThrbPV mice) also exhibit distinct phenotypes. These knockin mutant mice provide an opportunity to understand the molecular basis of isoform-dependent functions in vivo. Here we tested the hypothesis that the distinct functions of TR mutant isoforms are directed by a subset of nuclear regulatory proteins. Tandem-affinity chromatography of HeLa nuclear extracts showed that distinct 33 nuclear proteins including nuclear receptor corepressor (NCoR1) and six other proteins preferentially associated with TRα1PV or TRβ1PV, respectively. These results indicate that recruitment of nuclear regulatory proteins by TR mutants is subtype dependent. The involvement of NCoR1 in mediating the distinct liver phenotype of Thra1PV and ThrbPV mice was further explored. NCoR1 preferentially interacted with TRα1PV rather than with TRβ1PV. NCoR1 was recruited more avidly to the thyroid hormone response element-bound TRα1PV than to TRβ1PV in the promoter of the CCAAT/enhancer-binding protein α gene to repress its expression in the liver of Thra1PV mice, but not in ThrbPV mice. This preferential recruitment of NCoR1 by mutant isoforms could contribute, at least in part, to the distinct liver lipid phenotype of these mutant mice. The present study highlights a novel mechanism by which TR isoforms direct their selective functions via preferential recruitment of a subset of nuclear coregulatory proteins.

scholarly journals MITOCHONDRIA AS REVERSIBLE REGULATORS OF AGING ASSOCIATED SKIN WRINKLES AND HAIR LOSS IN MICE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S395-S395
Author(s):  
Keshav K Singh
Keyword(s):  
Mouse Model ◽  
Hair Loss ◽  
Transgene Expression ◽  
Skin Aging ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Dominant Negative Mutation ◽  
Polymerase Domain ◽  
Skin Wrinkles

Abstract To evaluate the consequences of the decline in mtDNA content associated with aging we have created an inducible mouse model expressing, in the polymerase domain of POLG1, a dominant-negative mutation that induces depletion of mtDNA. We utilized this inducible mouse model to modulate mitochondrial function by depleting and repleting the mtDNA content. We demonstrate that, in mice, ubiquitous expression of dominant-negative mutant POLG1 leads to 1) reduction of mtDNA content in skin, 2) skin wrinkles, and 3) hair loss. By turning off the mutant POLG1 transgene expression in the whole animal, the skin and hair phenotypes revert to normal after repletion of mtDNA. Thus, we have developed whole-animal mtDNA depleter-repleter mice. These mice present evidence that mtDNA homeostasis is involved in skin aging phenotype and loss of hair and provide an unprecedented opportunity to create tissue-specific mitochondrial modulation to determine the role of the mitochondria in a particular tissue.

Sign in / Sign up

Export Citation Format

Share Document