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Kun Yang, Yun Gao, Mingfu Yang, Zuoshang Xu, Qian Chen
Because the function of most non-coding (nc) RNAs is unknown, Cre-lox transgenic mice are useful tools to determine their functions in a tissue or developmental stage-specific manner. However, the technology faces challenges because expression of ncRNA-transgene lacks protein product. No antibody or peptide-tag can be used to trace ncRNA expression in mouse tissues in real time. Furthermore, transgene integration at different locus or orientations in the genome may result in recombination of genomic fragments in the Cre-lox system...
October 20, 2016: Connective Tissue Research
Laurel L Ballantyne, Yuan Yan Sin, Osama Y Al-Dirbashi, Xinzhi Li, David J Hurlbut, Colin D Funk
Arginase-1 (Arg1) converts arginine to urea and ornithine in the distal step of the urea cycle in liver. We previously generated a tamoxifen-inducible Arg1 deficient mouse model (Arg1-Cre) that disrupts Arg1 expression throughout the whole body and leads to lethality ≈ 2 weeks after gene disruption. Here, we evaluate if liver-selective Arg1 loss is sufficient to recapitulate the phenotype observed in global Arg1 knockout mice, as well as to gauge the effectiveness of gene delivery or hepatocyte transplantation to rescue the phenotype...
December 2016: Molecular Genetics and Metabolism Reports
Jia-Hai Chen
No abstract text is available yet for this article.
October 14, 2016: Otology & Neurotology
Toshifumi Nakamura, Isao Kurihara, Sakiko Kobayashi, Kenichi Yokota, Ayano Murai-Takeda, Yuko Mitsuishi, Mitsuha Morisaki, Nao Kohata, Yosuke Oshima, Gunther Schutz, Hirotaka Shibata, Hiroshi Itoh
OBJECTIVE: Recent studies have unveiled cardiovascular pathological roles of mineralocorticoid receptor (MR) in many types of cells. Although we have confirmed high expression of MR in intestinal epithelial cells (IEC), that role in progression of cardiovascular diseases is yet to be elucidated. As intestine is the first gate sensing sodium intake, MR of this organ is expected to have essential roles in blood pressure (BP) regulation. This study investigated the role of MR in IEC by using IEC-specific MR knockout mice (IEC-MR KO)...
September 2016: Journal of Hypertension
Gry Fluge Vindedal, Anna E Thoren, Vidar Jensen, Arne Klungland, Yong Zhang, Michael J Holtzman, Ole Petter Ottersen, Erlend A Nagelhus
There is a constitutive production of water in brain. The efflux routes of this excess water remain to be identified. We used basal brain water content as a proxy for the capacity of water exit routes. Basal brain water content was increased in mice with a complete loss of aquaporin-4 (AQP4) water channels (global Aqp4(-/-) mice), but not in mice with a selective removal of perivascular AQP4 or in a novel mouse line with a selective deletion of ependymal AQP4 (Foxj1-Cre-Aqp4(flox/flox) mice). Unique for the global Aqp4(-/-) mice is the loss of the AQP4 pool subjacent to the pial membrane...
October 14, 2016: Molecular and Cellular Neurosciences
D Reiss, R A Ceredig, T Secher, J Boué, F Barreau, G Dietrich, C Gavériaux-Ruff
BACKGROUND: Opiates act through opioid receptors to diminish pain. Here, we investigated whether mu (MOR) and delta (DOR) receptor endogenous activity assessed in the whole mouse body or in particular at peripheral receptors on primary nociceptive neurons, control colonic pain. METHODS: We compared global MOR and DOR receptor knockout (KO) mice, mice with a conditional deletion of MOR and DOR in Nav1.8-positive nociceptive primary afferent neurons (cKO), and control floxed mice of both genders for visceral sensitivity...
October 17, 2016: European Journal of Pain: EJP
Lili Ni, Hongchang Xie, Li Tan
The transcription factor FOXJ3 (Forkhead box J3) is highly expressed in spermatogonia and meiotic spermatocytes within mouse testes. Here, we addressed how FOXJ3 might participate in spermatogenesis using two conditional knockout mouse models in which the Foxj3 was deleted from either spermatogonia or meiotic spermatocytes. Both models exhibited complete male sterility, but distinct etiologies: Deleting FOXJ3 from spermatogonia using Foxj3(flox/flox) , Mvh-Cre mice caused Sertoli-cell-only syndrome in males...
October 14, 2016: Molecular Reproduction and Development
Naohiro Toda, Hideki Yokoi, Kiyoshi Mori, Masashi Mukoyama
CCN2 has been shown to be closely involved in the progression of renal fibrosis, indicating the potential of CCN2 inhibition as a therapeutic target. Although the examination of the phenotypes of adult CCN2 knockout mice with renal diseases has yielded valuable scientific insights, perinatal death has limited studies of CCN2 in vivo. Conditional knockout technology has become widely used for the deletion of genes in the desired cell populations and time points through the use of cell-specific Cre recombinase-expressing mice...
2017: Methods in Molecular Biology
Takashi Umehara, Ikko Kawashima, Tomoko Kawai, Yumi Hoshino, Ken-Ichirou Morohashi, Yuichi Shima, Wenxian Zeng, JoAnne S Richards, Masayuki Shimada
Adult Leydig cells are derived from proliferating stem/progenitor Leydig cells in the infant testis and subsequent differentiation to steroidogenic cells in adult mice. Leydig cell proliferation in the infant testis occurs primarily in response to increased levels of LH that induce Leydig cell expression of neuregulin 1, NRG1. Depletion of NRG1 in Nrg1 mutant mice (Nrg1(flox;flox); Cyp19a1Cre mice) dramatically reduces Leydig cell proliferation in the infant testes leading to reduction of testis weight, epididymial weight and serum testosterone in the adult mutant mice...
October 12, 2016: Endocrinology
Zhishan Luo, Sara Martí-Sànchez, Raquel Nafria, Gihan S Joshua, María de la Mata, Pablo Guardia, Cristina Flox, Carlos Martinez-Boubeta, Konstantinos Simeonidis, Jordi Llorca, Joan Ramon Morante, Jordi Arbiol, Maria Ibáñez, Andreu Cabot
The design and engineering of earth-abundant catalysts that are both cost-effective and highly active for water splitting is a crucial challenge in a number of energy conversion and storage technologies. In this direction, herein we report the synthesis of Fe3O4@NiFexOy core-shell nano-heterostructures and the characterization of their electrocatalytic performance toward the oxygen evolution reaction (OER). Such nanoparticles (NPs) were produced by a two-step synthesis procedure involving the colloidal synthesis of Fe3O4 nanocubes with a defective shell and the posterior diffusion of nickel cations within this defective shell...
October 12, 2016: ACS Applied Materials & Interfaces
Neele Schumacher, Stefanie Schmidt, Jeanette Schwarz, Dana Dohr, Juliane Lokau, Jürgen Scheller, Christoph Garbers, Athena Chalaris, Stefan Rose-John, Björn Rabe
Neutrophil and mononuclear cell infiltration during inflammatory processes is highly regulated. The first cells at the site of infection or inflammation are neutrophils, followed by mononuclear cells. IL-6 plays an important role during inflammatory states. It has been shown in several models that the soluble form of IL-6R (sIL-6R) is involved in the recruitment of mononuclear cells by a mechanism called IL-6 trans-signaling. It had been speculated that sIL-6R was generated at the site of inflammation by shedding from neutrophils via activation of the metalloprotease ADAM17...
October 3, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Nancy Lee, Carolyn E Rydyznski, Matthew S Rasch, Dennis S Trinh, A John MacLennan
Exogenous ciliary neurotrophic factor (CNTF) administration promotes the survival of motor neurons in a wide range of models. It also increases the expression of the critical neurotransmitter enzyme, choline acetyltransferase (ChAT), by in vitro motor neurons, likely independent of its effects on their survival. We have used the adult mouse facial nerve crush model and adult onset conditional disruption of the CNTF receptor α (CNTFRα) gene to directly examine the in vivo roles played by endogenous CNTF receptors in adult motor neuron survival and ChAT maintenance, independent of developmental functions...
September 26, 2016: Journal of Comparative Neurology
Yong Seon Choi, Ana Barbosa Marcondes de Mattos, Dan Shao, Tao Li, Miranda Nabben, Maengjo Kim, Wang Wang, Rong Tian, Stephen C Kolwicz
RATIONALE: Diastolic dysfunction is a common feature in many heart failure patients with preserved ejection fraction and has been associated with altered myocardial metabolism in hypertensive and diabetic patients.Therefore, metabolic interventions to improve diastolic function are warranted.In mice with a germline cardiac-specific deletion of acetyl CoA carboxylase 2 (ACC2), systolic dysfunction induced by pressure-overload was prevented by maintaining cardiac fatty acid oxidation (FAO)...
September 28, 2016: Journal of Molecular and Cellular Cardiology
Yianzhu Liu, Wenhao Chen, Chenglin Wu, Laurie J Minze, Jacek Z Kubiak, Xian C Li, Malgorzata Kloc, Rafik M Ghobrial
BACKGROUND: The cellular and molecular mechanisms of chronic rejection of transplanted organs remain obscure; however, macrophages are known to play a critical role in the injury and repair of allografts. Among multiple factors influencing macrophage infiltration to allografts, the fractalkine chemokine (C-X3-C motif) ligand 1(CX3CL1)/chemokine (C-X3-C motif) receptor 1 (CX3CR1) signaling pathway and actin cytoskeleton, which is regulated by a small guanosine-5׳-triphosphatase Ras homolog gene family member A (RhoA), are of the utmost importance...
August 20, 2016: Journal of Heart and Lung Transplantation
Zhongjian Xie, Yuan Yuan, Yi Jiang, Chandrama Shrestha, Ying Chen, Liyan Liao, Shangli Ji, Xiaoge Deng, Eryuan Liao, Daniel D Bikle
Previous studies have shown that dietary calcium suppresses oral carcinogenesis, but the mechanism is unclear. p120-catenin (p120) is a cytoplasmic protein closely associated with E-cadherin to form the E-cadherin-β-catenin complex and may function as a tumor suppressor in the oral epithelium. To determine whether p120 is involved in the mechanism by which dietary calcium suppresses oral carcinogenesis, The normal, low or high calcium diet was fed control mice (designated as floxed p120 mice) or mice in which p120 was specifically deleted in the oral squamous epithelium during the adult stage (designated as p120cKO mice)...
September 28, 2016: Journal of Cellular Physiology
Camille Attané, Marie-Line Peyot, Roxane Lussier, Pegah Poursharifi, Shangang Zhao, Dongwei Zhang, Johane Morin, Marco Pineda, Shupei Wang, Olivier Dumortier, Neil B Ruderman, Grant A Mitchell, Brigitte Simons, S R Murthy Madiraju, Erik Joly, Marc Prentki
AIMS/HYPOTHESIS: To directly assess the role of beta cell lipolysis in insulin secretion and whole-body energy homeostasis, inducible beta cell-specific adipose triglyceride lipase (ATGL)-deficient (B-Atgl-KO) mice were studied under normal diet (ND) and high-fat diet (HFD) conditions. METHODS: Atgl (flox/flox) mice were cross-bred with Mip-Cre-ERT mice to generate Mip-Cre-ERT(/+);Atgl (flox/flox) mice. At 8 weeks of age, these mice were injected with tamoxifen to induce deletion of beta cell-specific Atgl (also known as Pnpla2), and the mice were fed an ND or HFD...
September 27, 2016: Diabetologia
Ling-Lin Chen, Mei-Ling Wu, Feng Zhu, Jie-Jing Kai, Jing-Yin Dong, Xi-Mei Wu, Ling-Hui Zeng
AIMS: Previous study suggests that mTOR signaling pathway may play an important role in epileptogenesis. The present work was designed to explore the contribution of raptor protein to the development of epilepsy and comorbidities. METHODS: Mice with conditional knockout of raptor protein were generated by cross-bred Rptor(flox/flox) mice with nestin-CRE mice. The expression of raptor protein was analyzed by Western blotting in brain tissue samples. Neuronal death and mossy fiber sprouting were detected by FJB staining and Timm staining, respectively...
September 28, 2016: CNS Neuroscience & Therapeutics
Swen Hülsmann, Guillaume Mesuret, Julia Dannenberg, Mauricio Arnoldt, Marcus Niebert
Mutations in methyl-CpG-binding protein 2 (MECP2) gene have been shown to manifest in a neurodevelopmental disorder that is called Rett syndrome. A typical problem that occurs during development is a disturbance of breathing. To address the role of inhibitory neurons, we generated a mouse line that restores MECP2 in inhibitory neurons in the brainstem by crossbreeding a mouse line that expresses the Cre-recombinase (Cre) in inhibitory neurons under the control of the glycine transporter 2 (GlyT2, slc6a5) promotor (GlyT2-Cre) with a mouse line that has a floxed-stop mutation of the Mecp2 gene (Mecp2 (stop/y))...
2016: Frontiers in Physiology
Mu-En Lin, Theodore M Chen, Mary C Wallingford, Ngoc B Nguyen, Shunsuke Yamada, Chenphop Sawangmake, Jaimei Zhang, Mei Y Speer, Cecilia M Giachelli
AIMS: Vascular smooth muscle cells (SMCs) are major precursors contributing to osteochondrogenesis and calcification in atherosclerosis. Runt-related transcription factor-2 (Runx2) has been found essential for SMC differentiation to an osteochondrogenic phenotype and subsequent calcification in vitro A recent study using a conditional targeting allele that produced a truncated Runx2 protein in SMCs of ApoE(-/-) mice showed reduced vascular calcification, likely occurring via reduction of receptor activator of nuclear factor-κB ligand (RANKL), macrophage infiltration, and atherosclerotic lesion formation...
September 26, 2016: Cardiovascular Research
Junshuang Jia, Xiaolin Lin, Xia Lin, Taoyan Lin, Bangzhu Chen, Weichao Hao, Yushuang Cheng, Yu Liu, Meijuan Dian, Kaitai Yao, Dong Xiao, Weiwang Gu
The Cre/loxP system has become an important tool for the conditional gene knockout and conditional gene expression in genetically engineered mice. The applications of this system depend on transgenic reporter mouse lines that provide Cre recombinase activity with a defined cell type-, tissue-, or developmental stage-specificity. To develop a sensitive assay for monitoring Cre-mediated DNA excisions in mice, we generated Cre-mediated excision reporter mice, designated R/L mice (R/L: mRFP(monomeric red fluorescent protein)/luciferase), express mRFP throughout embryonic development and adult stages, while Cre-mediated excision deletes a loxP-flanked mRFP reporter gene and STOP sequence, thereby activating the expression of the second reporter gene luciferase, as assayed by in vivo and ex vivo bioluminescence imaging...
October 2016: Genome Génome / Conseil National de Recherches Canada
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