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https://www.readbyqxmd.com/read/29775750/the-effects-of-capn1-gene-inactivation-on-the-differential-expression-of-genes-in-skeletal-muscle
#1
William T Olive, Brittney N Keel, Amanda K Lindholm-Perry, Justyna Horodyska, Andrew P Foote
Protein turnover is required for muscle growth and regeneration and several proteolytic enzymes, including the calpains, degrade myofibrillar proteins during this process. In a previous experiment, phenotypic differences were observed between μ-calpain knockout (KO) and wild type (WT) mice, including nutrient accretion and fiber type differences. These changes were particularly evident as the animals aged. Thus, we utilized 18 mice (9 KO and 9 WT) to compare transcript abundance to identify differentially expressed genes (DEGs) at 52 wk of age...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775702/abnormal-sleep-architecture-and-hippocampal-circuit-dysfunction-in-a-mouse-model-of-fragile-x-syndrome
#2
Christine E Boone, Heydar Davoudi, Jon B Harrold, David J Foster
Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and single-gene cause of autism spectrum disorder. The Fmr1 null mouse models much of the human disease including hyperarousal, sensory hypersensitivity, seizure activity, and hippocampus-dependent cognitive impairment. Sleep architecture is disorganized in FXS patients, but has not been examined in Fmr1 knockout (Fmr1-KO) mice. Hippocampal neural activity during sleep, which is implicated in memory processing, also remains uninvestigated in Fmr1-KO mice...
May 15, 2018: Neuroscience
https://www.readbyqxmd.com/read/29775646/the-rna-binding-protein-ars2-supports-hematopoiesis-at-multiple-levels
#3
Seerat Elahi, Shawn M Egan, G Aaron Holling, Rachel L Kandefer, Michael J Nemeth, Scott H Olejniczak
Recent biochemical characterization of Arsenic resistance protein 2 (Ars2) has established it as central to determining the fate of nascent RNA polymerase II (RNAPII) transcripts. Through interactions with the nuclear 5'-7-methylguanosine (7mG) cap binding complex (CBC), Ars2 promotes co-transcriptional processing coupled with nuclear export or degradation of several classes of RNAPII transcripts, allowing for gene expression programs that facilitate rapid and sustained proliferation of immortalized cells in culture...
May 15, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29775615/extracellular-matrix-protein-dmp1-suppresses-osteogenic-differentiation-of-mesenchymal-stem-cells
#4
Shufan Zhang, Huixuan Wan, Peng Wang, Mengmeng Liu, Gongchen Li, Chunxue Zhang, Yao Sun
Mesenchymal Stem Cells (MSCs) are self-renewing and multipotent stem cells which was investigated for diverse clinical applications. However, complex mechanism of MSCs fate determination is still not fully disclosed. Extracellular matrix (ECM) proteins contribute to maintain MSCs stemness by providing extracellular microenvironment. Increasing evidences show that ECM proteins could also regulate the fate of MSCs directly. Dentin matrix protein 1 (DMP1) is an ECM protein enrich in bone tissue and terminal cells, which well-known in promoting osteoblasts and osteocytes maturation, and facilitate mineralization...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775613/suppression-of-nlrp3-inflammasome-attenuates-stress-induced-depression-like-behavior-in-nlgn3-deficient-mice
#5
Ze-Qun Li, Zhi-Yuan Yan, Bo-Jun Lan, Yi-Qun Dong, Ye Xiong
Depression, regulated by central nervous system (CNS), is a significant inflammatory disorder. Neuroligin3 (NLGN3) has been implicated in brain functions. In the study, a chronic unpredictable mild stress (CUMS) model in wild type (WT) or NLGN3-knockout (KO) mice was established to explore the role of NLGN3 in regulating depression and to reveal the underlying molecular mechanism. The results indicated that NLGN3-knockout markedly reversed the loss of body weight, the reduction of sucrose consumption, the decrease of immobile time in the forced swimming tests (FST) and tail suspension tests (TST) induced by CUMS paradigm...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775594/embryogenesis-and-adult-life-in-the-absence-of-intrinsic-apoptosis-effectors-bax-bak-and-bok
#6
Francine F S Ke, Hannah K Vanyai, Angus D Cowan, Alex R D Delbridge, Lachlan Whitehead, Stephanie Grabow, Peter E Czabotar, Anne K Voss, Andreas Strasser
Intrinsic apoptosis, reliant on BAX and BAK, has been postulated to be fundamental for morphogenesis, but its precise contribution to this process has not been fully explored in mammals. Our structural analysis of BOK suggests close resemblance to BAX and BAK structures. Notably, Bok-/- Bax-/- Bak-/- animals exhibited more severe defects and died earlier than Bax-/- Bak-/- mice, implying that BOK has overlapping roles with BAX and BAK during developmental cell death. By analyzing Bok-/- Bax-/- Bak-/- triple-knockout mice whose cells are incapable of undergoing intrinsic apoptosis, we identified tissues that formed well without this process...
May 17, 2018: Cell
https://www.readbyqxmd.com/read/29775453/ts-hsp70-induces-protective-immunity-against-trichinella-spiralis-infection-in-mouse-by-activating-dendritic-cells-through-tlr2-and-tlr4
#7
Rui Zhang, Qing Sun, Yi Chen, Ximeng Sun, Yuan Gu, Zhang Zhao, Yuli Cheng, Limei Zhao, Jingjing Huang, Bin Zhan, Xinping Zhu
BACKGROUND: Trichinellosis is a serious food-borne parasitic zoonosis worldwide. In the effort to develop vaccine against Trichinella infection, we have identified Trichinella spiralis Heat shock protein 70 (Ts-Hsp70) elicits partial protective immunity against T. spiralis infection via activating dendritic cells (DCs) in our previous study. This study aims to investigate whether DCs were activated by Ts-Hsp70 through TLR2 and/or TLR4 pathways. METHODS AND FINDINGS: After blocking with anti-TLR2 and TLR4 antibodies, the binding of Ts-Hsp70 to DCs was significantly reduced...
May 18, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29774879/-role-of-dna-methyltransferase-1-in-mouse-skin-aging
#8
Xiangmei Ren, Xiao Xiao, Ben Wang, Yiya Zhang, Mei Yi, Ji Li, Wei Shi
To explore the role ofDNA methyltransferase 1 (DNMT1) in mouse skin aging.
 Methods: Epidermal conditional K14 Cre-mediated DNA methyltransferase 1 (DNMT1) knockout mice (Mut group, n=4) and the littermate normal mice with the same age (WT group) n=4) were used in this study. HE staining was used to detect the pathological changes of skin; the changes of number in the dermal elastic fibers were detected by Gomori aldehyde fuchsin staining, the number of 5-bromo-2-deoxyuridine (BrdU)-labeled transit amplifying cells (TAC) in epidermis were detected by immunohistochemical staining; the number of chlorodeoxyuridine (CldU)-label-retaining cells (LRC) in epidermis were detected by immunofluorescent staining...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29774542/accelerated-pre-senile-systemic-amyloidosis-in-pacap-knockout-mice-a-protective-role-of-pacap-in-age-related-degenerative-processes
#9
Dora Reglodi, Adel Jungling, Rémi Longuespée, Joerg Kriegsmann, Rita Casadonte, Mark Kriegsmann, Tamas Juhasz, Sebastian Bardosi, Andrea Tamas, Balazs Daniel Fulop, Krisztina Kovacs, Zsuzsanna Nagy, Jason Sparks, Attila Miseta, Gabriel Mazzucchelli, Hitoshi Hashimoto, Attila Bardosi
Dysregulation of neuropeptides may play an important role in aging-induced impairments. Among them, pituitary adenylate cyclase activating polypeptide (PACAP) is a potent cytoprotective peptide that provides an endogenous control against a variety of tissue-damaging stimuli. We hypothesized that the progressive decline of PACAP throughout life, and the well-known general cytoprotective effects of PACAP lead to age-related pathophysiological changes in PACAP deficiency, supported by the increased vulnerability to various stressors of animals partially or totally lacking PACAP...
May 17, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29774507/ap180-n-terminal-homology-anth-and-epsin-n-terminal-homology-enth-domains-physiological-functions-and-involvement-in-disease
#10
Sho Takatori, Taisuke Tomita
The AP180 N-terminal homology (ANTH) and Epsin N-terminal homology (ENTH) domains are crucially involved in membrane budding processes. All the ANTH/ENTH-containing proteins share the phosphoinositide-binding activity and can interact with clathrin or its related proteins via multiple binding motifs. Their function also include promotion of clathrin assembly, induction of membrane curvature, and recruitment of various effector proteins, such as those involved in membrane fission. Furthermore, they play a role in the sorting of specific cargo proteins, thereby enabling the cargos to be accurately transported and function at their appropriate locations...
May 18, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29774231/semaphorin3a-signaling-is-dispensable-for-motor-axon-reinnervation-of-the-adult-neuromuscular-junction
#11
Jennifer L Shadrach, Brian A Pierchala
The neuromuscular junction (NMJ) is a specialized synapse that is formed by motor axon innervation of skeletal muscle fibers. The maintenance of motor-muscle connectivity is critical for the preservation of muscle tone and generation of movement. Injury can induce a robust regenerative response in motor axons, but severe trauma or chronic denervation resulting from neurodegenerative disease typically leads to inefficient repair and poor functional recovery. The axon guidance molecule Semaphorin3A (Sema3A) has been implicated as a negative regulator of motor innervation...
May 2018: ENeuro
https://www.readbyqxmd.com/read/29774023/ferritin-h-deficiency-in-myeloid-compartments-dysregulates-host-energy-metabolism-and-increases-susceptibility-to-mycobacterium-tuberculosis-infection
#12
Vineel P Reddy, Krishna C Chinta, Vikram Saini, Joel N Glasgow, Travis D Hull, Amie Traylor, Fernanda Rey-Stolle, Miguel P Soares, Rajhmun Madansein, Md Aejazur Rahman, Coral Barbas, Kievershen Nargan, Threnesan Naidoo, Pratistadevi K Ramdial, James F George, Anupam Agarwal, Adrie J C Steyn
Iron is an essential factor for the growth and virulence of Mycobacterium tuberculosis ( Mtb) . However, little is known about the mechanisms by which the host controls iron availability during infection. Since ferritin heavy chain (FtH) is a major intracellular source of reserve iron in the host, we hypothesized that the lack of FtH would cause dysregulated iron homeostasis to exacerbate TB disease. Therefore, we used knockout mice lacking FtH in myeloid-derived cell populations to study Mtb disease progression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773976/facing-the-challenges-of-neuropeptide-gene-knockouts-why-do-they-not-inhibit-reproduction-in-adult-teleost-fish
#13
REVIEW
Vance L Trudeau
Genetic manipulation of teleost endocrine systems started with transgenic overexpression of pituitary growth hormone. Such strategies enhance growth and reduce fertility, but the fish still breed. Genome editing using transcription activator-like effector nuclease in zebrafish and medaka has established the role of follicle stimulating hormone for gonadal development and luteinizing hormone for ovulation. Attempts to genetically manipulate the hypophysiotropic neuropeptidergic systems have been less successful...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29773887/varacin-1-a-novel-analog-of-varacin-c-induces-p53-independent-apoptosis-in-cancer-cells-through-ros-mediated-reduction-of-xiap
#14
Jing Zhou, Wen-Li Li, Zi-Xuan Wang, Nai-Yuan Chen, Yue Tang, Xiao-Xiao Hu, Jing-Huan Deng, Yixin Lu, Guo-Dong Lu
Varacin C is a promising anticancer agent and possesses acid-promoted and photo-induced DNA-damaging activities. In this study, we synthesized an analog varacin-1 (VCA-1) and examined its anticancer potentials. The results demonstrated that VCA-1 caused dose-dependent apoptotic cell death in cancer cells. Note that this action is independent of p53 status, because VCA-1 induced similar levels of apoptosis in two different panels of cell lines (HCT116 p53- wild-type vs. HCT116 p53-knockout colon cancer cells, and p53-expressing U2OS vs...
May 17, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29773874/mutations-in-six-nephrosis-genes-delineate-a-pathogenic-pathway-amenable-to-treatment
#15
Shazia Ashraf, Hiroki Kudo, Jia Rao, Atsuo Kikuchi, Eugen Widmeier, Jennifer A Lawson, Weizhen Tan, Tobias Hermle, Jillian K Warejko, Shirlee Shril, Merlin Airik, Tilman Jobst-Schwan, Svjetlana Lovric, Daniela A Braun, Heon Yung Gee, David Schapiro, Amar J Majmundar, Carolin E Sadowski, Werner L Pabst, Ankana Daga, Amelie T van der Ven, Johanna M Schmidt, Boon Chuan Low, Anjali Bansal Gupta, Brajendra K Tripathi, Jenny Wong, Kirk Campbell, Kay Metcalfe, Denny Schanze, Tetsuya Niihori, Hiroshi Kaito, Kandai Nozu, Hiroyasu Tsukaguchi, Ryojiro Tanaka, Kiyoshi Hamahira, Yasuko Kobayashi, Takumi Takizawa, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Naonori Kumagai, Kazumoto Iijima, Henry Fehrenbach, Jameela A Kari, Sherif El Desoky, Sawsan Jalalah, Radovan Bogdanovic, Nataša Stajić, Hildegard Zappel, Assel Rakhmetova, Sharon-Rose Wassmer, Therese Jungraithmayr, Juergen Strehlau, Aravind Selvin Kumar, Arvind Bagga, Neveen A Soliman, Shrikant M Mane, Lewis Kaufman, Douglas R Lowy, Mohamad A Jairajpuri, Richard P Lifton, York Pei, Martin Zenker, Shigeo Kure, Friedhelm Hildebrandt
No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773865/perlecan-a-heparan-sulfate-proteoglycan-regulates-systemic-metabolism-with-dynamic-changes-in-adipose-tissue-and-skeletal-muscle
#16
Yuri Yamashita, Satoshi Nakada, Toshinori Yoshihara, Takeshi Nara, Norihiko Furuya, Takashi Miida, Nobutaka Hattori, Eri Arikawa-Hirasawa
Perlecan (HSPG2), a heparan sulfate proteoglycan, is a component of basement membranes and participates in a variety of biological activities. Here, we show physiological roles of perlecan in both obesity and the onset of metabolic syndrome. The perinatal lethality-rescued perlecan knockout (Hspg2-/- -Tg) mice showed a smaller mass and cell size of white adipose tissues than control (WT-Tg) mice. Abnormal lipid deposition, such as fatty liver, was not detected in the Hspg2-/- -Tg mice, and those mice also consumed more fat as an energy source, likely due to their activated fatty acid oxidation...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773834/embryonic-pou5f1-is-required-for-expanded-bovine-blastocyst-formation
#17
Bradford W Daigneault, Sandeep Rajput, George W Smith, Pablo J Ross
POU5F1 is a transcription factor and master regulator of cell pluripotency with indispensable roles in early embryo development and cell lineage specification. The role of embryonic POU5F1 in blastocyst formation and cell lineage specification differs between mammalian species but remains completely unknown in cattle. The CRISPR/Cas9 system was utilized for targeted disruption of the POU5F1 gene by direct injection into zygotes. Disruption of the bovine POU5F1 locus prevented blastocyst formation and was associated with embryonic arrest at the morula stage...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773831/dnajc17-is-localized-in-nuclear-speckles-and-interacts-with-splicing-machinery-components
#18
A Pascarella, G Ferrandino, S C Credendino, C Moccia, F D'Angelo, B Miranda, C D'Ambrosio, P Bielli, O Spadaro, M Ceccarelli, A Scaloni, C Sette, M De Felice, G De Vita, E Amendola
DNAJC17 is a heat shock protein (HSP40) family member, identified in mouse as susceptibility gene for congenital hypothyroidism. DNAJC17 knockout mouse embryos die prior to implantation. In humans, germline homozygous mutations in DNAJC17 have been found in syndromic retinal dystrophy patients, while heterozygous mutations represent candidate pathogenic events for myeloproliferative disorders. Despite widespread expression and involvement in human diseases, DNAJC17 function is still poorly understood. Herein, we have investigated its function through high-throughput transcriptomic and proteomic approaches...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773802/cd4-t-cells-are-activated-in-regional-lymph-nodes-and-migrate-to-skin-to-initiate-lymphedema
#19
Gabriela D García Nores, Catherine L Ly, Daniel A Cuzzone, Raghu P Kataru, Geoffrey E Hespe, Jeremy S Torrisi, Jung Ju Huang, Jason C Gardenier, Ira L Savetsky, Matthew D Nitti, Jessie Z Yu, Sonia Rehal, Babak J Mehrara
T cell-mediated responses have been implicated in the development of fibrosis, impaired lymphangiogenesis, and lymphatic dysfunction in secondary lymphedema. Here we show that CD4+ T cells are necessary for lymphedema pathogenesis by utilizing adoptive transfer techniques in CD4 knockout mice that have undergone tail skin and lymphatic excision or popliteal lymph node dissection. We also demonstrate that T cell activation following lymphatic injury occurs in regional skin-draining lymph nodes after interaction with antigen-presenting cells such as dendritic cells...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773687/the-role-of-intercalated-cell-nedd4-2-in-bp-regulation-ion-transport-and-transporter-expression
#20
Masayoshi Nanami, Truyen D Pham, Young Hee Kim, Baoli Yang, Roy L Sutliff, Olivier Staub, Janet D Klein, Karen I Lopez-Cayuqueo, Regine Chambrey, Annie Y Park, Xiaonan Wang, Vladimir Pech, Jill W Verlander, Susan M Wall
Background Nedd4-2 is an E3 ubiquitin-protein ligase that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a correlation between Nedd4-2 and BP. In this study, we explored the effect of intercalated cell (IC) Nedd4-2 gene ablation on IC transporter abundance and function and on BP. Methods We generated IC Nedd4-2 knockout mice using Cre-lox technology and produced global pendrin/ Nedd4-2 null mice by breeding global Nedd4-2 null ( Nedd4-2-/- ) mice with global pendrin null ( Slc26a4-/- ) mice...
May 17, 2018: Journal of the American Society of Nephrology: JASN
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