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https://www.readbyqxmd.com/read/29227996/generation-and-phenotypic-characterisation-of-a-cytochrome-p450-4x1-knockout-mouse
#1
Himanshu Kharkwal, Farhat Batool, Frank Koentgen, David R Bell, David A Kendall, Francis J P Ebling, Ian R Duce
Cytochrome P450 4x1 (Cyp4x1) is expressed at very high levels in the brain but the function of this protein is unknown. It has been hypothesised to regulate metabolism of fatty acids and to affect the activity of endocannabinoid signalling systems, which are known to influence appetite and energy metabolism. The objective of the present investigation was to determine the impact of Cyp4x1 on body weight and energy metabolism by developing a line of transgenic Cyp4x1-knock out mice. Mice were developed with a global knock-out of the gene; the full-length RNA was undetectable, and mice were viable and fertile...
2017: PloS One
https://www.readbyqxmd.com/read/29223537/rankl-signaling-sustains-primary-tumor-growth-in-genetically-engineered-mouse-models-of-lung-adenocarcinoma
#2
Julien Faget, Caroline Contat, Nadine Zangger, Solange Peters, Etienne Meylan
HYPOTHESIS: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality. Recent retrospective clinical analyses suggest that blocking the receptor activator of NF-κB (RANK) signaling pathway inhibits the growth of NSCLC and might represent a new treatment strategy. METHODS: RANK and RANKL expression in human lung adenocarcinoma was interrogated from publicly available gene expression datasets. Several genetically engineered mouse models were used to evaluate treatment efficacy of RANK-Fc to block RANKL, with primary tumor growth measured longitudinally using micro-computed tomography...
December 6, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29220094/osteocytes-play-an-important-role-in-experimental-periodontitis-in-healthy-and-diabetic-mice-through-expression-of-rankl
#3
Dana T Graves, Ahmed Alshabab, Mayra Laino Albiero, Marcelo Mattos, Joice Dias Correa, Shanshan Chen, Yang Yang
AIM: Periodontitis results from bacteria induced inflammation. A key cytokine, RANKL is produced by a number of cell types. The cellular source of RANKL critical for periodontitis has not been established. METHODS: We induced periodontal bone loss by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in both normoglycemic and streptozotocin induced type 1 diabetic mice. Experimental transgenic mice had osteocyte specific deletion of floxed RANKL mediated by DMP-1 driven Cre recombinase...
December 8, 2017: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/29218825/in-vivo-evidence-supporting-a-metastasis-suppressor-role-for-stard13-dlc2-in-erbb2-neu-oncogene-induced-mouse-mammary-tumours
#4
Pratima Basak, Heather Leslie, Rachelle L Dillon, William J Muller, Afshin Raouf, Michael Ra Mowat
Overexpression of dominant oncogenes and the loss of tumor suppressor genes are basic genetic events in the acquisition of the malignant phenotype. The erb-b2 receptor tyrosine kinase 2 (ERBB-2) proto-oncogene is overexpressed in 20-30% of human breast cancers. The StAR related lipid transfer domain containing 13 gene (STARD13), also known as Deleted in Liver Cancer-2 (DLC-2), maps to chromosome band 13q12.3 and is frequently downregulated in human cancers, including 72% of breast cancers. It encodes a RhoGAP protein with sterile α motif (SAM) and StAR-related lipid transfer (START) domains...
December 8, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29217477/activation-of-hepatic-nogo-b-receptor-expression-a-new-anti-liver-steatosis-mechanism-of-statins
#5
Wenwen Zhang, Xiaoxiao Yang, Yuanli Chen, Wenquan Hu, Lipei Liu, Xiaomeng Zhang, Mengyang Liu, Lei Sun, Ying Liu, Miao Yu, Xiaoju Li, Luyuan Li, Yan Zhu, Qing Robert Miao, Jihong Han, Yajun Duan
Deficiency of hepatic Nogo-B receptor (NgBR) expression activates liver X receptor α (LXRα) in an adenosine monophosphate-activated protein kinase α (AMPKα)-dependent manner, thereby inducing severe hepatic lipid accumulation and hypertriglyceridemia. Statins have been demonstrated non-cholesterol lowering effects including anti-nonalcoholic fatty liver disease (NAFLD). Herein, we investigated if the anti-NAFLD function of statins depends on activation of NgBR expression. In vivo, atorvastatin protected apoE deficient or NgBR floxed, but not hepatic NgBR deficient mice, against Western diet (WD)-increased triglyceride levels in liver and serum...
December 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29214672/region-specific-deletions-of-the-glutamate-transporter-glt1-differentially-affect-seizure-activity-and-neurodegeneration-in-mice
#6
Junya Sugimoto, Moeko Tanaka, Kaori Sugiyama, Yukiko Ito, Hidenori Aizawa, Miho Soma, Tomoko Shimizu, Akira Mitani, Kohichi Tanaka
Glial glutamate transporter GLT1 plays a key role in the maintenance of extracellular glutamate homeostasis. Recent human genetic studies have suggested that de novo mutations in GLT1 (EAAT2) cause early-onset epilepsy with multiple seizure types. Consistent with these findings, global GLT1 null mice show lethal spontaneous seizures. The consequences of GLT1 dysfunction vary between different brain regions, suggesting that the role of GLT1 dysfunction in epilepsy may also vary with brain regions. In this study, we generated region-specific GLT1 knockout mice by crossing floxed-GLT1 mice with mice that express the Cre recombinase in a particular domain of the ventricular zone...
December 6, 2017: Glia
https://www.readbyqxmd.com/read/29209313/unconventional-pro-inflammatory-cd4-t-cell-response-in-b-cell-deficient-mice-infected-with-trypanosoma-cruzi
#7
Melisa Gorosito Serrán, Jimena Tosello Boari, Facundo Fiocca Vernengo, Cristian G Beccaría, María C Ramello, Daniela A Bermejo, Amelia G Cook, Carola G Vinuesa, Carolina L Montes, Eva V Acosta Rodriguez, Adriana Gruppi
Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29208611/perturbations-of-nad-salvage-systems-impact-mitochondrial-function-and-energy-homeostasis-in-mouse-myoblasts-and-intact-skeletal-muscle
#8
Marianne Agerholm, Morten Dall, Benjamin A H Jensen, Clara Prats, Søren Madsen, Astrid L Basse, Anne-Sofie Graae, Steve Risis, Julie Goldenbaum, Bjørn Quistorff, Steen Larsen, Sara G Vienberg, Jonas T Treebak
Nicotinamide adenine dinucleotide (NAD+) can be synthesized by nicotinamide phosphoribosyltransferase (NAMPT). We aimed to determine the role of NAMPT for maintaining NAD+ levels, mitochondrial function, and metabolic homeostasis in skeletal muscle cells. We generated stable Nampt knockdown (shNampt KD) C2C12 cells using a shRNA lentiviral approach. Moreover, we applied gene electrotransfer to express cre recombinase in tibialis anterior muscle of floxed Nampt mice. In shNampt KD C2C12 myoblasts, Nampt and NAD+ levels were reduced by 70% and 50%, respectively, and maximal respiratory capacity was reduced by 25%...
December 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29204184/viral-cre-loxp-tools-aid-genome-engineering-in-mammalian-cells
#9
Ranjita Sengupta, Amy Mendenhall, Nandita Sarkar, Chandreyee Mukherjee, Amirali Afshari, Joseph Huang, Biao Lu
Background: Targeted nucleases have transformed genome editing technology, providing more efficient methods to make targeted changes in mammalian genome. In parallel, there is an increasing demand of Cre-LoxP technology for complex genome manipulation such as large deletion, addition, gene fusion and conditional removal of gene sequences at the target site. However, an efficient and easy-to-use Cre-recombinase delivery system remains lacking. Results: We designed and constructed two sets of expression vectors for Cre-recombinase using two highly efficient viral systems, the integrative lentivirus and non-integrative adeno associated virus...
2017: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29203237/adiponectin-release-and-insulin-receptor-targeting-share-trans-golgi-dependent-endosomal-trafficking-routes
#10
Maria Rödiger, Martin W Werno, Ilka Wilhelmi, Christian Baumeier, Deike Hesse, Nina Wettschureck, Stefan Offermanns, Kyungyeun Song, Michael Krauß, Annette Schürmann
OBJECTIVE: Intracellular vesicle trafficking maintains cellular structures and functions. The assembly of cargo-laden vesicles at the trans-Golgi network is initiated by the ARF family of small GTPases. Here, we demonstrate the role of the trans-Golgi localized monomeric GTPase ARFRP1 in endosomal-mediated vesicle trafficking of mature adipocytes. METHODS: Control (Arfrp1flox/flox) and inducible fat-specific Arfrp1 knockout (Arfrp1iAT-/-) mice were metabolically characterized...
November 22, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29202854/neuronal-ccl2-expression-drives-inflammatory-monocyte-infiltration-into-the-brain-during-acute-virus-infection
#11
Charles L Howe, Reghann G LaFrance-Corey, Emma N Goddery, Renee K Johnson, Kanish Mirchia
BACKGROUND: Viral encephalitis is a dangerous compromise between the need to robustly clear pathogen from the brain and the need to protect neurons from bystander injury. Theiler's murine encephalomyelitis virus (TMEV) infection of C57Bl/6 mice is a model of viral encephalitis in which the compromise results in hippocampal damage and permanent neurological sequelae. We previously identified brain-infiltrating inflammatory monocytes as the primary driver of this hippocampal pathology, but the mechanisms involved in recruiting these cells to the brain were unclear...
December 4, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29195058/essential-role-of-ift140-in-promoting-dentinogenesis
#12
G Li, M Liu, S Zhang, H Wan, Q Zhang, R Yue, X Yan, X Wang, Z Wang, Y Sun
Primary cilia, with highly regulated cellular sensory functions, play key roles in tissue development and function maintenance. Intraflagellar transport 140 (IFT140) is a subunit of IFT complex A, which is specialized for retrograde transportation in cilia. Mutations of Ift140 are usually associated with syndromic ciliopathy and may cause isolated diseases such as retinal dystrophy, short ribs, and polycystic kidney. However, the role of IFT140 in tooth development has not been well investigated. In this study, a close relationship between IFT140 and dentin formation is disclosed...
November 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29193599/characterization-of-mice-carrying-a-conditional-tead1-allele
#13
Tong Wen, Qin Yin, Luyi Yu, Guoqing Hu, Jinhua Liu, Wei Zhang, Liang Huang, Huabo Su, Menghong Wang, Jiliang Zhou
The Hippo-YAP pathway is essential for controlling organ size and tumorigenesis. Previous studies have demonstrated that the primary outcome of YAP signaling in the nucleus is achieved by interaction with the transcription factor TEAD1. The YAP/TEAD1 complex binds to DNA element and regulates the expression of genes involved in cell growth. However, constitutive knockout of TEAD1 leads to early embryonic lethality in mice. Thus, generation of a floxed TEAD1 mouse becomes crucial for further understanding mid- to late-gestation and post-natal role of TEAD1...
November 30, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/29174640/dorsal-raph%C3%A3-nucleus-glucocorticoid-receptors-inhibit-tph2-gene-expression-in-male-c57bl-6j-mice
#14
Melanie Y Vincent, Nina C Donner, David G Smith, Christopher A Lowry, Lauren Jacobson
The serotonergic dorsal raphé nucleus (DRN) expresses glucocorticoid receptors (GR), and systemic glucocorticoids have been shown to regulate expression and activity of tryptophan hydroxylase isoform 2, the rate-limiting enzyme for serotonin synthesis in brain. We have used intra-DRN injection of pseudotyped adeno-associated virus AAV2/9 transducing either green fluorescent protein (GFP control) or Cre recombinase (DRN GR deletion) in floxed GR mice to determine if DRN GR directly regulate DRN mRNA levels of tryptophan hydroxylase 2 (tph2)...
November 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29165602/deletion-of-connective-tissue-growth-factor-ameliorates-peritoneal-fibrosis-by-inhibiting-angiogenesis-and-inflammation
#15
Naohiro Toda, Kiyoshi Mori, Masato Kasahara, Kenichi Koga, Akira Ishii, Keita P Mori, Keisuke Osaki, Masashi Mukoyama, Motoko Yanagita, Hideki Yokoi
Background: Connective tissue growth factor (CTGF/CCN2) regulates the signalling of other growth factors and promotes fibrosis. CTGF is increased in mice and humans with peritoneal fibrosis. Inhibition of CTGF has not been examined as a potential therapeutic target for peritoneal fibrosis because systemic CTGF knockout mice die at the perinatal stage. Methods: To study the role of CTGF in peritoneal fibrosis of adult mice, we generated CTGF conditional knockout (cKO) mice by crossing CTGF floxed mice with RosaCreERT2 mice...
November 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29163805/thymine-dna-glycosylase-tdg-is-involved-in-the-pathogenesis-of-intestinal-tumors-with-reduced-apc-expression
#16
Jinfei Xu, Salvatore Cortellino, Rossella Tricarico, Wen-Chi Chang, Gabrielle Scher, Karthik Devarajan, Michael Slifker, Robert Moore, Maria Rosaria Bassi, Elena Caretti, Margie Clapper, Harry Cooper, Alfonso Bellacosa
Thymine DNA Glycosylase (TDG) is a base excision repair enzyme that acts as a thymine and uracil DNA N-glycosylase on G:T and G:U mismatches, thus protecting CpG sites in the genome from mutagenesis by deamination. In addition, TDG has an epigenomic function by removing the novel cytosine derivatives 5-formylcytosine and 5-carboxylcytosine (5caC) generated by Ten-Eleven Translocation (TET) enzymes during active DNA demethylation. We and others previously reported that TDG is essential for mammalian development...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29158846/subcellular-localization-of-survivin-determines-its-function-in-cardiomyocytes
#17
Tien-Jui Tsang, Ying-Chang Hsueh, Erika I Wei, David J Lundy, Bill Cheng, You-Tzung Chen, Shoei-Shen Wang, Patrick C H Hsieh
Rationale: Reducing cardiomyocyte death and enhancing their proliferation after myocardial infarction is perhaps the single largest challenge for cardiac tissue regeneration. Survivin (SVV) is the smallest member of the inhibitor of apoptosis (IAP) family but plays two important roles; inhibiting caspase-9 activation in the intrinsic apoptosis pathway, and regulating microtubule dynamics and chromosome segregation during cell division. Genetic depletion of cardiac SVV leads to incomplete cardiomyocyte division and abnormal heart development...
2017: Theranostics
https://www.readbyqxmd.com/read/29158577/vgf-function-in-depression-and-antidepressant-efficacy
#18
C Jiang, W-J Lin, M Sadahiro, B Labonté, C Menard, M L Pfau, C A Tamminga, G Turecki, E J Nestler, S J Russo, S R Salton
Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158260/the-actin-organizing-formin-protein-fhod3-is-required-for-postnatal-development-and-functional-maintenance-of-the-adult-heart-in-mice
#19
Tomoki Ushijima, Noriko Fujimoto, Sho Matsuyama, Meikun Kan-O, Hiroshi Kiyonari, Go Shioi, Yohko Kage, Sho Yamasaki, Ryu Takeya, Hideki Sumimoto
Cardiac development and function require actin-myosin interactions in the sarcomere, a highly organized contractile structure. Sarcomere assembly mediated by formin homology 2 domain-containing 3 (Fhod3), a member of formins that direct formation of straight actin filaments, is essential for embryonic cardiogenesis. However, the role of Fhod3 in the neonatal and adult stages has remained unknown. Here we generated floxed Fhod3 mice to bypass the embryonic lethality of an Fhod3 knockout (KO). Perinatal KO of Fhod3 in the heart caused juvenile lethality at around day 10 after birth with enlarged hearts composed of severely impaired myofibrils, indicating that Fhod3 is crucial for postnatal heart development...
November 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29157305/evaluation-of-the-effect-of-a-floxed-neo-cassette-within-the-dystroglycan-dag1-gene
#20
Francesca Sciandra, Bianca Maria Scicchitano, Giulia Signorino, Maria Giulia Bigotti, Barbara Tavazzi, Francesca Lombardi, Manuela Bozzi, Gigliola Sica, Bruno Giardina, Sandra Blaess, Andrea Brancaccio
OBJECTIVE: Dystroglycan (DG) is an adhesion complex formed by two subunits, α-DG and β-DG. In skeletal muscle, DG is part of the dystrophin-glycoprotein complex that is crucial for sarcolemma stability and it is involved in a plethora of muscular dystrophy phenotypes. Due to the important role played by DG in skeletal muscle stability as well as in a wide variety of other tissues including brain and the peripheral nervous system, it is essential to investigate its genetic assembly and transcriptional regulation...
November 21, 2017: BMC Research Notes
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