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https://www.readbyqxmd.com/read/28819283/the-c-terminal-multimerization-domain-is-essential-for-leukemia-development-by-cbf%C3%AE-smmhc-in-a-mouse-knockin-model
#1
L Zhao, H Alkadi, E M Kwon, T Zhen, J Lichtenberg, L Alemu, J Cheng, A D Friedman, P P Liu
Leukemia accepted article preview online, 18 August 2017. doi:10.1038/leu.2017.262.
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28815492/building-cre-knockin-rat-lines-using-crispr-cas9
#2
Yuanwu Ma, Lianfeng Zhang, Xingxu Huang
Conditional gene inactivation strategy helps researchers to study the gene functions that are critical in embryogenesis or in defined tissues of adulthood. The Cre/loxP system is widely used for conditional gene inactivation/activation in cells or organisms. Cre knockin animal lines are essential for gene expression or inactivation in a spatially and temporally restricted manner. However, to generate a Cre knockin line by traditional approach is laborious. Recently, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) has been proven as a simple and efficient genome-editing tool...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28794128/dynamic-changes-in-h1-subtype-composition-during-epigenetic-reprogramming
#3
Annalisa Izzo, Céline Ziegler-Birling, Peter W S Hill, Lydia Brondani, Petra Hajkova, Maria-Elena Torres-Padilla, Robert Schneider
In mammals, histone H1 consists of a family of related proteins, including five replication-dependent (H1.1-H1.5) and two replication-independent (H1.10 and H1.0) subtypes, all expressed in somatic cells. To systematically study the expression and function of H1 subtypes, we generated knockin mouse lines in which endogenous H1 subtypes are tagged. We focused on key developmental periods when epigenetic reprogramming occurs: early mouse embryos and primordial germ cell development. We found that dynamic changes in H1 subtype expression and localization are tightly linked with chromatin remodeling and might be crucial for transitions in chromatin structure during reprogramming...
August 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28791777/mutations-in-the-katnb1-gene-cause-left-right-asymmetry-and-heart-defects
#4
M B Furtado, D J Merriner, S Berger, D Rhodes, D Jamsai, M K O'Bryan
BACKGROUND: The microtubule-severing protein complex katanin is composed two subunits, the ATPase subunit, KATNA1, and the non-catalytic regulatory subunit, KATNB1. Recently, the Katnb1 gene has been linked to infertility, regulation of centriole and cilia formation in fish and mammals, as well as neocortical brain development. KATNB1 protein is expressed in germ cells in humans and mouse, mitotic/meiotic spindles and cilia, although the full expression pattern of the Katnb1 gene has not been described...
August 9, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28768901/essential-role-for-ccr6-in-certain-inflammatory-diseases-demonstrated-using-specific-antagonist-and-knockin-mice
#5
Remy Robert, Caroline Ang, Guizhi Sun, Laurent Juglair, Ee X Lim, Linda J Mason, Natalie L Payne, Claude Ca Bernard, Charles R Mackay
The chemokine receptor CCR6 marks subsets of T cells and innate lymphoid cells that produce IL-17 and IL-22, and as such may play a role in the recruitment of these cells to certain inflammatory sites. However, the precise role of CCR6 has been controversial, in part because no effective monoclonal antibody (mAb) inhibitors against this receptor exist for use in mouse models of inflammation. We circumvented this problem using transgenic mice expressing human CCR6 (hCCR6) under control of its native promoter (hCCR6-Tg/mCCR6-/-)...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28763160/crispr-cas9-mediated-targeting-of-the-rosa26-locus-produces-cre-reporter-rat-strains-for-monitoring-cre-loxp-mediated-lineage-tracing
#6
Yuanwu Ma, Lei Yu, Shuo Pan, Shan Gao, Wei Chen, Xu Zhang, Wei Dong, Jing Li, Rui Zhou, Lan Huang, Yunlin Han, Lin Bai, Li Zhang, Lianfeng Zhang
The rat is an important laboratory animal for physiological, toxicological and pharmacological studies. CRISPR/Cas9 is a simple and efficient tool to generate precise genetic modifications in rats, which will promote the accumulation of rat genetic resources and enable more precise studies of gene function. To monitor Cre/loxP-mediated excision in vivo, we generated a Cre reporter rat strain (Rosa26-imCherry) by knockin of a Cre reporter cassette at Rosa26 locus using CRISPR/Cas9. Rosa26-imCherry rats exhibited inducible expression of the mCherry cassette (imCherry) using the Cre/loxP system, whereas normal rats exhibited ubiquitous expression of eGFP but not mCherry in the whole body...
August 1, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28760161/mutation-induced-loss-of-app-function-causes-gabaergic-depletion-in-recessive-familial-alzheimer-s-disease-analysis-of-osaka-mutation-knockin-mice
#7
Tomohiro Umeda, Tetsuya Kimura, Kayo Yoshida, Keizo Takao, Yuki Fujita, Shogo Matsuyama, Ayumi Sakai, Minato Yamashita, Yuki Yamashita, Kiyouhisa Ohnishi, Mamiko Suzuki, Hiroshi Takuma, Tsuyoshi Miyakawa, Akihiko Takashima, Takashi Morita, Hiroshi Mori, Takami Tomiyama
The E693Δ (Osaka) mutation in APP is linked to familial Alzheimer's disease. While this mutation accelerates amyloid β (Aβ) oligomerization, only patient homozygotes suffer from dementia, implying that this mutation is recessive and causes loss-of-function of amyloid precursor protein (APP). To investigate the recessive trait, we generated a new mouse model by knocking-in the Osaka mutation into endogenous mouse APP. The produced homozygous, heterozygous, and non-knockin littermates were compared for memory, neuropathology, and synaptic plasticity...
July 31, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28749013/physiological-versus-pharmacological-signalling-to-myosin-phosphorylation-in-airway-smooth-muscle
#8
Ning Gao, Ming-Ho Tsai, Audrey N Chang, Weiqi He, Cai-Ping Chen, Minsheng Zhu, Kristine E Kamm, James T Stull
Ca(2+) /calmodulin activation of myosin light chain kinase (MLCK) initiates myosin regulatory light chain (RLC) phosphorylation for smooth muscle contraction with subsequent dephosphorylation for relaxation by myosin light chain phosphatase (MLCP) containing regulatory (MYPT1) and catalytic (PP1cδ) subunits. RLC phosphorylation-dependent force development is regulated by distinct signalling modules involving protein phosphorylations. We investigated responses to cholinergic agonist treatment versus neurostimulation by electric field stimulation (EFS) in bovine tracheal smooth muscle...
July 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28737513/loss-of-function-mutations-in-co-chaperone-bag3-destabilize-small-hsps-and-cause-cardiomyopathy
#9
Xi Fang, Julius Bogomolovas, Tongbin Wu, Wei Zhang, Canzhao Liu, Jennifer Veevers, Matthew J Stroud, Zhiyuan Zhang, Xiaolong Ma, Yongxin Mu, Dieu-Hung Lao, Nancy D Dalton, Yusu Gu, Celine Wang, Michael Wang, Yan Liang, Stephan Lange, Kunfu Ouyang, Kirk L Peterson, Sylvia M Evans, Ju Chen
Defective protein quality control (PQC) systems are implicated in multiple diseases. Molecular chaperones and co-chaperones play a central role in functioning PQC. Constant mechanical and metabolic stress in cardiomyocytes places great demand on the PQC system. Mutation and downregulation of the co-chaperone protein BCL-2-associated athanogene 3 (BAG3) are associated with cardiac myopathy and heart failure, and a BAG3 E455K mutation leads to dilated cardiomyopathy (DCM). However, the role of BAG3 in the heart and the mechanisms by which the E455K mutation leads to DCM remain obscure...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28728075/immunological-tolerance-as-a-barrier-to-protective-hiv-humoral-immunity
#10
REVIEW
Kristin Ms Schroeder, Amanda Agazio, Raul M Torres
HIV-1 infection typically eludes antibody control by our immune system and is not yet prevented by a vaccine. While many viral features contribute to this immune evasion, broadly neutralizing antibodies (bnAbs) against HIV-1 are often autoreactive and it has been suggested that immunological tolerance may restrict a neutralizing antibody response. Indeed, recent Ig knockin mouse studies have shown that bnAb-expressing B cells are largely censored by central tolerance in the bone marrow. However, the contribution of peripheral tolerance in limiting the HIV antibody response by anergic and potentially protective B cells is poorly understood...
July 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28727987/associations-of-autoimmunity-immunodeficiency-lymphomagenesis-and-gut-microbiota-in-mice-with-knockins-for-a-pathogenic-autoantibody
#11
Shweta Jain, Jerrold M Ward, Dong-Mi Shin, Hongsheng Wang, Zohreh Naghashfar, Alexander L Kovalchuk, Herbert C Morse
A number of mouse strains transgenic for B-cell receptors specific for nucleic acids or other autoantigens have been generated to understand how autoreactive B cells are regulated in normal and autoimmune mice. Previous studies of nonautoimmune C57BL/6 mice heterozygous for both the IgH and IgL knockins of the polyreactive autoantibody, 564, produced high levels of autoantibodies in a largely Toll-like receptor 7-dependent manner. Herein, we describe studies of mice homozygous for the knockins that also expressed high levels of autoantibodies but, unlike the heterozygotes, exhibited a high incidence of mature B-cell lymphomas and enhanced susceptibility to bacterial infections...
July 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28723571/emi2-is-essential-for-mouse-spermatogenesis
#12
Lakshmi Gopinathan, Radoslaw Szmyd, Diana Low, M Kasim Diril, Heng-Yu Chang, Vincenzo Coppola, Kui Liu, Lino Tessarollo, Ernesto Guccione, Ans M M van Pelt, Philipp Kaldis
The meiotic functions of Emi2, an inhibitor of the APC/C complex, have been best characterized in oocytes where it mediates metaphase II arrest as a component of the cytostatic factor. We generated knockout mice to determine the in vivo functions of Emi2-in particular, its functions in the testis, where Emi2 is expressed at high levels. Male and female Emi2 knockout mice are viable but sterile, indicating that Emi2 is essential for meiosis but dispensable for embryonic development and mitotic cell divisions...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28716990/proof-of-principle-for-a-novel-class-of-antihypertensives-that-target-the-oxidative-activation-of-protein-kinase-g-i%C3%AE
#13
Joseph R Burgoyne, Oleksandra Prysyazhna, Daniel A Richards, Philip Eaton
Arterial hypertension continues to be a major health burden. Development of new antihypertensive drugs that engage vasodilatory mechanisms not harnessed by available therapies offer therapeutic potential. Oxidants induce an interprotein disulfide in protein kinase G Iα (PKG Iα) at C42, which is associated with its targeting and activation, resulting in vasodilation and blood pressure lowering. Consequently, we developed an assay and screened for electrophilic drugs that activate PKG Iα by selectively targeting C42, as such compounds have potential as novel antihypertensives with a mechanism of action that differs from current therapies...
July 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28714144/cerebellins-are-differentially-expressed-in-selective-subsets-of-neurons-throughout-the-brain
#14
Erica Seigneur, Thomas C Südhof
Cerebellins are secreted hexameric proteins that form tripartite complexes with the presynaptic cell-adhesion molecules neurexins or 'deleted-in-colorectal-cancer', and the postsynaptic glutamate-receptor-related proteins GluD1 and GluD2. These tripartite complexes are thought to regulate synapses. However, cerebellins are expressed in multiple isoforms whose relative distributions and overall functions are not understood. Three of the four cerebellins, Cbln1, Cbln2, and Cbln4, autonomously assemble into homohexamers, whereas the Cbln3 requires Cbln1 for assembly and secretion...
July 16, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28710355/high-resolution-imaging-of-dna-methylation-dynamics-using-a-zebrafish-reporter
#15
Ranran Zhang, Lian Liu, Yuxiao Yao, Fei Fei, Feng Wang, Qian Yang, Yonghao Gui, Xu Wang
As one of the major epigenetic modifications, DNA methylation is constantly regulated during embryonic development, cell lineage commitment, and pathological processes. To facilitate real-time observation of DNA methylation, we generated a transgenic zebrafish reporter of DNA methylation (zebraRDM) via knockin of an mCherry-fused methyl-CpG binding domain (MBD) probe driven by the bactin2 promoter. The probe colocalized with heterochromatin, and its intensity was positively correlated with 5 mC immunostaining at a subcellular resolution in early embryos...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684956/knockin-out-the-spasms
#16
COMMENT
Libor Velíšek
No abstract text is available yet for this article.
May 2017: Epilepsy Currents
https://www.readbyqxmd.com/read/28675425/foxc2-influences-alveolar-epithelial-cell-differentiation-during-lung-development
#17
Mayoko Tsuji, Masae Morishima, Kazuhiko Shimizu, Shunichi Morikawa, Mikael Heglind, Sven Enerbäck, Taichi Ezaki, Jun Tamaoki
FOXC2, a forkhead transcriptional factor, is a candidate gene for congenital heart diseases and lymphedema-distichiasis syndrome and yellow nail syndrome; however, there are no reports on Foxc2 and the development of the lung. We have identified lung abnormalities in Foxc2-knockout embryos during investigation of cardiac development. The aim of this study was to clarify the morphological characteristics during lung development using ICR-Foxc2 knockout lungs. Mutant fetuses at embryonic days 10.5-18.5 were obtained from mating of Foxc2(+/-) mice and then analyzed...
July 4, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28671867/knockin-on-heaven-s-door-end-of-life-decisions-and-discussions
#18
Curt Tribble Md
More than 2.5 million people die in the United States each year. For the majority who live out their final days in various institutions or in hospice care, decisions must be made about which treatments to administer, which treatments to stop, which treatments to continue, and which treatments to back off of. Thus, while death remains inevitable, its timing is often very much a function of human agency. Once it was common to speak of "nature taking its course," but now it has become as common to view death as something about which people have some control [Meisel 2008]...
June 29, 2017: Heart Surgery Forum
https://www.readbyqxmd.com/read/28654070/generation-of-genetically-modified-mice-through-the-microinjection-of-oocytes
#19
Fabien Delerue, Lars M Ittner
The use of genetically modified mice has significantly contributed to studies on both physiological and pathological in vivo processes. The pronuclear injection of DNA expression constructs into fertilized oocytes remains the most commonly used technique to generate transgenic mice for overexpression. With the introduction of CRISPR technology for gene targeting, pronuclear injection into fertilized oocytes has been extended to the generation of both knockout and knockin mice. This work describes the preparation of DNA for injection and the generation of CRISPR guides for gene targeting, with a particular emphasis on quality control...
June 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#20
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
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