The Experts below are selected from a list of 176619 Experts worldwide ranked by ideXlab platform
Claudine H. Kos - One of the best experts on this subject based on the ideXlab platform.
-
Cre/loxP system for generating tissue-specific Knockout Mouse models.
Nutrition Reviews, 2004Co-Authors: Claudine H. KosAbstract:Alteration of the Mouse genome by conventional transgenic and gene-targeted approaches has greatly facilitated studies of gene function. However, a gene alteration expressed in the germ line may cause an embryonic lethal phenotype resulting in no viable Mouse to study gene function. Similarly, a gene alteration may exert its effect in multiple different cell and tissue types, creating a complex phenotype in which it is difficult to distinguish direct function in a particular tissue from secondary effects resulting from altered gene function in other tissues. Therefore, methods have been developed to control conditions such as the timing, cell-type, and tissue specificity of gene activation or repression. This brief review provides an overview of the Cre/LoxP system for generating tissue-specific Knockout Mouse models.
-
Methods in Nutrition Science: Cre/loxP System for Generating Tissue-specific Knockout Mouse Models
Nutrition Reviews, 2004Co-Authors: Claudine H. KosAbstract:Editor's note: From time to time, we take the opportunity in Nutrition Reviews to highlight a particularly exciting application of sophisticated methodological advances that are relevant to the nutrition research community. In the current issue of Nutrition Reviews , Dr. Claudine Kos has provide a brief review of some of the salient features of the Cre/loxP system for generating tissue-specific Knockout Mouse models. Hopefully, this review will provide additional background to Dr. George Wolf's Brief Critical Review (page 253) of the use of the Cre/loxP technique by investigators to gain further insight into the function of the peroxysome proliferators-activated receptor-gamma (PPAR-γ), as well as promote its further use within experimental nutrition. Alteration of the Mouse genome by conventional transgenic and gene-targeted approaches has greatly facilitated studies of gene function. However, a gene alteration expressed in the germ line may cause an embryonic lethal phenotype resulting in no viable Mouse to study gene function. Similarly, a gene alteration may exert its effect in multiple different cell and tissue types, creating a complex phenotype in which it is difficult to distinguish direct function in a particular tissue from secondary effects resulting from altered gene function in other tissues. Therefore, methods have been developed to control conditions such as the timing, cell-type, and tissue specificity of gene activation or repression. This brief review provides an overview of the Cre/LoxP system for generating tissue-specific Knockout Mouse models .
Chu-xia Deng - One of the best experts on this subject based on the ideXlab platform.
-
Conditional Knockout Mouse models of cancer.
Cold Spring Harbor protocols, 2014Co-Authors: Chu-xia DengAbstract:Abstract In 2007, three scientists, Drs. Mario R. Capecchi, Martin J. Evans, and Oliver Smithies, received the Nobel Prize in Physiology or Medicine for their contributions of introducing specific gene modifications into mice. This technology, commonly referred to as gene targeting or Knockout, has proven to be a powerful means for precisely manipulating the mammalian genome and has generated great impacts on virtually all phases of mammalian biology and basic biomedical research. Of note, germline mutations of many genes, especially tumor suppressors, often result in lethality during embryonic development or at developmental stages before tumor formation. This obstacle has been effectively overcome by the use of conditional Knockout technology in conjunction with Cre-LoxP- or Flp-Frt-mediated temporal and/or spatial systems to generate genetic switches for precise DNA recombination. Currently, numerous conditional Knockout Mouse models have been successfully generated and applied in studying tumor initiation, progression, and metastasis. This review summarizes some conditional mutant Mouse models that are widely used in cancer research and our understanding of the possible mechanisms underlying tumorigenesis.
-
Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional Knockout Mouse skin.
Oncogene, 2005Co-Authors: Wenhui Qiao, Philip Owens, Xin Wang, Chu-xia DengAbstract:Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional Knockout Mouse skin
-
Knockout Mouse models and mammary tumorigenesis.
Seminars in cancer biology, 2001Co-Authors: Chu-xia Deng, Steven G. BrodieAbstract:The generation of transgenic mice overexpressing activated forms of oncogenes has greatly advanced our understanding into their roles in mammary tumor initiation, promotion and progression. However, targeted disruption of tumor suppressor genes often results in lethality at stages prior to mammary tumor formation. This obstacle can now be overcome using several approaches including conditional Knockouts that delete genes of interest in a spatial and temporal manner. This review summarizes recent studies on tumor suppressor genes, including APC, ATM, BRCA1, BRCA2, PTEN and p53, in Knockout Mouse models and our understanding of the possible mechanisms underlying mammary tumorigenesis.
Samir N. P. Kelada - One of the best experts on this subject based on the ideXlab platform.
-
Baseline and innate immune response characterization of a Zfp30 Knockout Mouse strain
Mammalian Genome, 2020Co-Authors: Lucas T. Laudermilk, Adelaide Tovar, Alison K. Homstad, Joseph M. Thomas, Kathryn M. Mcfadden, Miriya K. Tune, Dale O. Cowley, Jason R. Mock, Folami Ideraabdullah, Samir N. P. KeladaAbstract:Airway neutrophilia is correlated with disease severity in a number of chronic and acute pulmonary diseases, and dysregulation of neutrophil chemotaxis can lead to host tissue damage. The gene Zfp30 was previously identified as a candidate regulator of neutrophil recruitment to the lungs and secretion of CXCL1, a potent neutrophil chemokine, in a genome-wide mapping study using the Collaborative Cross. ZFP30 is a putative transcriptional repressor with a KRAB domain capable of inducing heterochromatin formation. Using a CRISPR-mediated Knockout Mouse model, we investigated the role that Zfp30 plays in recruitment of neutrophils to the lung using models of allergic airway disease and acute lung injury. We found that the Zfp30 null allele did not affect CXCL1 secretion or neutrophil recruitment to the lungs in response to various innate immune stimuli. Intriguingly, despite the lack of neutrophil phenotype, we found there was a significant reduction in the proportion of live Zfp30 homozygous female mutant mice produced from heterozygous matings. This deviation from the expected Mendelian ratios implicates Zfp30 in fertility or embryonic development. Overall, our results indicate that Zfp30 is an essential gene but does not influence neutrophilic inflammation in this particular Knockout model.
-
Baseline and Innate Immune Response Characterization of a Zfp30 Knockout Mouse Strain
2020Co-Authors: Lucas T. Laudermilk, Adelaide Tovar, Alison K. Homstad, Joseph M. Thomas, Kathryn M. Mcfadden, Miriya K. Tune, Dale O. Cowley, Jason R. Mock, Folami Ideraabdullah, Samir N. P. KeladaAbstract:Airway neutrophilia is correlated with disease severity in a number of chronic and acute pulmonary diseases, and dysregulation of neutrophil chemotaxis can lead to host tissue damage. The gene Zfp30 was previously identified as a candidate regulator of neutrophil recruitment to the lungs and secretion of CXCL1, a potent neutrophil chemokine, in a genome-wide mapping study using the Collaborative Cross. ZFP30 is a putative transcriptional repressor with a KRAB domain capable of inducing heterochromatin formation. Using a CRISPR-mediated Knockout Mouse model, we investigated the role that Zfp30 plays in recruitment of neutrophils to the lung using models of allergic airway disease and acute lung injury. We found that the Zfp30 null allele did not affect CXCL1 secretion or neutrophil recruitment to the lungs in response to various innate immune stimuli. Intriguingly, despite the lack of neutrophil phenotype, we found there was a significant reduction in the proportion of live Zfp30 homozygous mutant mice produced from heterozygous matings. This deviation from the expected mendelian inheritance (i.e. transmission ratio distortion) implicates Zfp30 in fertility or embryonic development. Overall, our results indicate that Zfp30 is an essential gene but does not influence neutrophilic inflammation in this particular Knockout model.
Steven U Walkley - One of the best experts on this subject based on the ideXlab platform.
-
neuropathology of the mcoln1 Knockout Mouse model of mucolipidosis type iv
Journal of Neuropathology and Experimental Neurology, 2009Co-Authors: Matthew C Micsenyi, Kostantin Dobrenis, Gloria Stephney, James Pickel, Marie T Vanier, Susan A Slaugenhaupt, Steven U WalkleyAbstract:The recently developed Mcoln1 -/- Knockout Mouse provides a novel model for analyzing mucolipin 1 function and mucolipidosis type IV disease. Here we characterize the neuropathology of Mcoln1 -/- Mouse at the end stage. Evidence of ganglioside accumulation, including increases in GM2, GM3, and GD3 and redistribution of GM1, was found throughout the central nervous system (CNS) independent of significant cholesterol accumulation. Unexpectedly, colocalization studies using immunofluorescence confocal microscopy revealed that GM1 and GM2 were present in separate vesicles within individual neurons. While GM2 was significantly colocalized with LAMP2, consistent with late-endosomal/ lysosomal processing, some GM2-immunoreactivity occurred in LAMP2-negative sites, suggesting involvement of other vesicular systems. P62/Sequestosome 1 (P62/SQSTM1) inclusions were also identified in the CNS of the Mcoln1 -/- Mouse, suggesting deficiencies in protein degradation. Glial cell activation was increased in brain, and there was evidence of reduced myelination in cerebral and cerebellar white matter tracts. Autofluorescent material accumulated throughout the brains of the Knockout mice. Finally, axonal spheroids were prevalent in white matter tracts and Purkinje cell axons. This neuropathological characterization of the Mcoln1 -/- Mouse provides an important step in understanding how mucolipin 1 loss of function affects the CNS and contributes to mucolipidosis type IV disease.
-
Neuropathology of the Mcoln1(-/-) Knockout Mouse model of mucolipidosis type IV.
Journal of neuropathology and experimental neurology, 2009Co-Authors: Matthew C Micsenyi, Kostantin Dobrenis, Gloria Stephney, James Pickel, Marie T Vanier, Susan A Slaugenhaupt, Steven U WalkleyAbstract:The recently developed Mcoln1 -/- Knockout Mouse provides a novel model for analyzing mucolipin 1 function and mucolipidosis type IV disease. Here we characterize the neuropathology of Mcoln1 -/- Mouse at the end stage. Evidence of ganglioside accumulation, including increases in GM2, GM3, and GD3 and redistribution of GM1, was found throughout the central nervous system (CNS) independent of significant cholesterol accumulation. Unexpectedly, colocalization studies using immunofluorescence confocal microscopy revealed that GM1 and GM2 were present in separate vesicles within individual neurons. While GM2 was significantly colocalized with LAMP2, consistent with late-endosomal/ lysosomal processing, some GM2-immunoreactivity occurred in LAMP2-negative sites, suggesting involvement of other vesicular systems. P62/Sequestosome 1 (P62/SQSTM1) inclusions were also identified in the CNS of the Mcoln1 -/- Mouse, suggesting deficiencies in protein degradation. Glial cell activation was increased in brain, and there was evidence of reduced myelination in cerebral and cerebellar white matter tracts. Autofluorescent material accumulated throughout the brains of the Knockout mice. Finally, axonal spheroids were prevalent in white matter tracts and Purkinje cell axons. This neuropathological characterization of the Mcoln1 -/- Mouse provides an important step in understanding how mucolipin 1 loss of function affects the CNS and contributes to mucolipidosis type IV disease.
Fumihiko Fukamauchi - One of the best experts on this subject based on the ideXlab platform.
-
Preprotachykinin A and cholecystokinin mRNAs in tenascin-gene Knockout Mouse brain.
Neuropeptides, 1997Co-Authors: Fumihiko Fukamauchi, M KusakabeAbstract:Tenascin (TN), an extracellular matrix glycoprotein, exhibits various functions in the developmental stage of the mammalian brain. TN-gene deficient mice show abnormal behavior such as hyperlocomotion and poor swimming ability, and this abnormal behavior may derive from a low level of dopamine transmission in the striatum or hippocampus of the TN-gene disrupted Mouse brain. We assayed preprotachykinin A (PPT) and cholecystokinin (CCK) mRNAs in the terminal fields of the dopamine neuron. The levels of PPT mRNA were significantly higher in the striatum, and the expression of CCK mRNA was markedly augmented in the hippocampus of the TN-Knockout mice, compared to the wild or heterozygous mice. One possible explanation of the changes of PPT and CCK mRNA expressions is functional compensation against the low level of dopamine turnover rate in the TN-Knockout Mouse brain.
-
Abnormal Behavior and Neurotransmissions of Tenascin Gene Knockout Mouse
Biochemical and biophysical research communications, 1996Co-Authors: Fumihiko Fukamauchi, Nobuko Mataga, Yi-jun Wang, Shigeo Sato, Atsushi Yoshiki, Moriaki KusakabeAbstract:Abstract To examine the role of tenascin (TN)in vivo,we have produced mice in which the TN gene is inactivated. In behavioral studies, TN-Knockout mice showed abnormal behavior such as hyperlocomotion and poor swimming ability. Biochemical analysis revealed that serotonin (5-HT) and dopamine (DA) transmission was decreased in the cerebral cortex, the hippocampus, or the striatum of TN-Knockout Mouse brain. The intraperitoneal administration of the DA receptor agonist, LY171555 (0.5 mg/kg, BW), inhibited the hyperlocomotion, and swimming behavior was transiently improved by the treatment with the 5-HT receptor agonist, 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride. These findings suggest that TN may play an important role in neurotransmissions related to behavior.
