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https://www.readbyqxmd.com/read/28335584/atrap-expression-in-brown-adipose-tissue-does-not-influence-the-development-of-diet-induced-metabolic-disorders-in-mice
#1
Kohji Ohki, Hiromichi Wakui, Kengo Azushima, Kazushi Uneda, Sona Haku, Ryu Kobayashi, Kotaro Haruhara, Sho Kinguchi, Miyuki Matsuda, Masato Ohsawa, Akinobu Maeda, Shintaro Minegishi, Tomoaki Ishigami, Yoshiyuki Toya, Akio Yamashita, Satoshi Umemura, Kouichi Tamura
Activation of tissue renin-angiotensin system (RAS), mainly mediated by an angiotensin II (Ang II) type 1 receptor (AT1R), plays an important role in the development of obesity-related metabolic disorders. We have shown that AT1R-associated protein (ATRAP), a specific binding protein of AT1R, functions as an endogenous inhibitor to prevent excessive activation of tissue RAS. In the present study, we newly generated ATRAP/Agtrap-floxed (ATRAP(fl/fl)) mice and adipose tissue-specific ATRAP downregulated (ATRAP(adipoq)) mice by the Cre/loxP system using Adipoq-Cre...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28331060/proximal-tubule-glutamine-synthetase-expression-is-necessary-for-the-normal-response-to-dietary-protein-restriction
#2
Hyun-Wook Lee, Gunars Osis, Mary E Handlogten, Jill W Verlander, I David Weiner
Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and ¬decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of NH4+ and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28304136/zebrafish-models-of-non-canonical-wnt-planar-cell-polarity-signalling-fishing-for-valuable-insight-into-vertebrate-polarized-cell-behavior
#3
REVIEW
Maria Jussila, Brian Ciruna
Planar cell polarity (PCP) coordinates the uniform orientation, structure and movement of cells within the plane of a tissue or organ system. It is beautifully illustrated in the polarized arrangement of bristles and hairs that project from specialized cell surfaces of the insect abdomen and wings, and pioneering genetic studies using the fruit fly, Drosophila melanogaster, have defined a core signalling network underlying PCP. This core PCP/non-canonical Wnt signalling pathway is evolutionarily conserved, and studies in zebrafish have helped transform our understanding of PCP from a peculiarity of polarized epithelia to a more universal cellular property that orchestrates a diverse suite of polarized cell behaviors that are required for normal vertebrate development...
March 17, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28300205/one-step-generation-of-mice-carrying-a-conditional-allele-together-with-an-ha-tag-insertion-for-the-delta-opioid-receptor
#4
Dongru Su, Min Wang, Chenli Ye, Jiahui Fang, Yanhui Duan, Zhenghong Zhang, Qiuhong Hua, Changjie Shi, Lihong Zhang, Ru Zhang, Xin Xie
G protein-coupled receptors (GPCRs) are important modulators of many physiological functions and excellent drug targets for many diseases. However, to study the functions of endogenous GPCRs is still a challenging task, partially due to the low expression level of GPCRs and the lack of highly potent and selective GPCR antibodies. Overexpression or knock-in of tagged GPCRs, or knockout of specific GPCRs in mice, are common strategies used to study the in vivo functions of these receptors. However, generating separate mice carrying tagged GPCRs or conditional alleles for GPCRs is labor intensive, and requires additional breeding costs...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293728/oligodendrocyte-precursor-cells-in-the-mouse-optic-nerve-originate-in-the-preoptic-area
#5
Katsuhiko Ono, Kengo Yoshii, Hiroyuki Tominaga, Hitoshi Gotoh, Tadashi Nomura, Hirohide Takebayashi, Kazuhiro Ikenaka
The present study aims to examine the origin of oligodendrocyte progenitor cells (OPCs) in the mouse optic nerve (ON) by labeling OPCs in the fetal forebrain. The labeling of OPCs in the ON was performed by injection of a retrovirus vector carrying the lacZ gene into the lateral ventricle, or by inducible Cre/loxP of Olig2-positive cells. The retrovirus labeling revealed that ventricular zone-derived cells of the fetal forebrain relocated to the ON and differentiated into oligodendrocytes. In addition, lineage tracing of Olig2-positive cells and whole-mount staining of PDGFRα-positive cells demonstrated that OPCs appeared by E12...
March 14, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28284715/hyaluronan-binding-protein-involved-in-hyaluronan-depolymerization-controls-endochondral-ossification-through-hyaluronan-metabolism
#6
Masayuki Shimoda, Hiroyuki Yoshida, Sakiko Mizuno, Toru Hirozane, Keisuke Horiuchi, Yuta Yoshino, Hideaki Hara, Yae Kanai, Shintaro Inoue, Muneaki Ishijima, Yasunori Okada
Hyaluronan (HA) plays an important role in the development and maintenance of tissues, and its degradation is implicated in many pathologic conditions. We recently reported that HA-binding protein involved in HA depolymerization (HYBID/KIAA1199; encoded by CEMIP) is a key molecule in HA depolymerization, but its developmental and pathologic functions remain elusive. We generated Hybid-deficient mice using the Cre/locus of crossover in P1 (loxP) system and analyzed their phenotypes. Hybid-deficient mice were viable and fertile, but their adult long bones were shorter than those of wild-type animals...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28278197/the-role-of-platelet-and-endothelial-garp-in-thrombosis-and-hemostasis
#7
Elien Vermeersch, Frederik Denorme, Wim Maes, Simon F De Meyer, Karen Vanhoorelbeke, Justin Edwards, Ethan M Shevach, Derya Unutmaz, Hodaka Fujii, Hans Deckmyn, Claudia Tersteeg
BACKGROUND: Glycoprotein-A Repetitions Predominant protein (GARP or LRRC32) is present on among others human platelets and endothelial cells. Evidence for its involvement in thrombus formation was suggested by full knockout of GARP in zebrafish. OBJECTIVES: To evaluate the role of GARP in platelet physiology and in thrombus formation using platelet and endothelial conditional GARP knock out mice. METHODS: Platelet and endothelial specific GARP knockout mice were generated using the Cre-loxP recombination system...
2017: PloS One
https://www.readbyqxmd.com/read/28271437/cellular-and-circuitry-bases-of-autism-lessons-learned-from-the-temporospatial-manipulation-of-autism-genes-in-the-brain
#8
REVIEW
Samuel W Hulbert, Yong-Hui Jiang
Transgenic mice carrying mutations that cause Autism Spectrum Disorders (ASDs) continue to be valuable for determining the molecular underpinnings of the disorders. Recently, researchers have taken advantage of such models combined with Cre-loxP and similar systems to manipulate gene expression over space and time. Thus, a clearer picture is starting to emerge of the cell types, circuits, brain regions, and developmental time periods underlying ASDs. ASD-causing mutations have been restricted to or rescued specifically in excitatory or inhibitory neurons, different neurotransmitter systems, and cells specific to the forebrain or cerebellum...
April 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28271037/cholinergic-neurons-in-the-dorsomedial-hypothalamus-regulate-food-intake
#9
Jae Hoon Jeong, Dong Kun Lee, Young-Hwan Jo
OBJECTIVE: Central cholinergic neural circuits play a role in the regulation of feeding behavior. The dorsomedial hypothalamus (DMH) is considered the appetite-stimulating center and contains cholinergic neurons. Here, we study the role of DMH cholinergic neurons in the control of food intake. METHODS: To selectively stimulate DMH cholinergic neurons, we expressed stimulatory designer receptors exclusively activated by designer drugs (DREADDs) and channelrhodopsins in DMH cholinergic neurons by injection of adeno-associated virus (AAV) vectors into the DMH of choline acetyltransferase (ChAT)-IRES-Cre mice...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28267623/thymic-nf-%C3%AE%C2%BAb-inducing-kinase-nik-regulates-cd4-t-cell-elicited-liver-injury-and-fibrosis-in-mice
#10
Hong Shen, Liang Sheng, Yi Xiong, Yeung-Hyen Kim, Lin Jiang, Zheng Chen, Yong Liu, Kalyani Pyaram, Cheong-Hee Chang, Liangyou Rui
BACKGROUND & AIMS: The liver is an immunologically-privileged organ. Breakdown of liver immune privilege has been reported in chronic liver disease; however, the role of adaptive immunity in liver injury is poorly defined. NIK is known to regulate immune tissue development, but its role in maintaining liver homeostasis remains unknown. This study aimed to assess the role of NIK, particularly thymic NIK, in regulating liver adaptive immunity. METHODS: NIK was deleted systemically or conditionally using the cre/loxp system...
March 3, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28258144/construction-of-bacillus-thuringiensis-simulant-strains-suitable-for-environmental-release
#11
Sangjin Park, Changhwan Kim, Daesang Lee, Dong Hyun Song, Ki Cheol Cheon, Hong Suk Lee, Seong Joo Kim, Jee Cheon Kim, Sang Yup Lee
For a surrogate bacterium to be used in outdoor studies, it is important to consider environmental and human safety, and ease of detection. Recently, Bacillus thuringiensis, a popular bioinsecticide bacterium, is gaining attention as a surrogate bacterium for its use in biodefense. In this study, we constructed simulant strains of B. thuringiensis with enhanced characteristics for environmental studies. Through transposon mutagenesis, pigment genes were inserted into the chromosome, producing yellow-colored colonies for easy detection...
March 3, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28252198/cre-loxp-mediated-recombination-general-principles-and-experimental-considerations
#12
Micheal A McLellan, Nadia A Rosenthal, Alexander R Pinto
The cre-loxP-mediated recombination system (the "cre-loxP system") is an integral experimental tool for mammalian genetics and cell biology. Use of the system has greatly expanded our ability to precisely interrogate gene function in the mouse, providing both spatial and temporal control of gene expression. This has been largely due to the simplicity of its use and its adaptability to address diverse biological questions. While the use of the cre-loxP system is becoming increasingly widespread, in particular because of growing availability of conditional mouse mutants, many considerations need to be taken into account when utilizing the cre-loxP system...
March 2, 2017: Current Protocols in Mouse Biology
https://www.readbyqxmd.com/read/28242773/adipose-specific-deletion-of-kif5b-exacerbates-obesity-and-insulin-resistance-in-a-mouse-model-of-diet-induced-obesity
#13
Ju Cui, Jing Pang, Ya-Jun Lin, Huan Gong, Zhen-He Wang, Yun-Xuan Li, Jin Li, Zai Wang, Ping Jiang, Da-Peng Dai, Jian Li, Jian-Ping Cai, Jian-Dong Huang, Tie-Mei Zhang
Recent studies have shown that KIF5B (conventional kinesin heavy chain) mediates glucose transporter type 4 translocation and adiponectin secretion in 3T3-L1 adipocytes, suggesting an involvement of KIF5B in the homeostasis of metabolism. However, the in vivo physiologic function of KIF5B in adipose tissue remains to be determined. In this study, adipose-specific Kif5b knockout (F-K5bKO) mice were generated using the Cre-LoxP strategy. F-K5bKO mice had similar body weights to controls fed on a standard chow diet...
February 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28224202/germline-specific-dgcr8-knockout-in-zebrafish-using-a-back-approach
#14
Yun Liu, Zeyao Zhu, Idy H T Ho, Yujian Shi, Yuxin Xie, Jianzhen Li, Yong Zhang, Matthew T V Chan, Christopher H K Cheng
Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28219987/a-unique-angiotensin-sensitive-neuronal-population-coordinates-neuroendocrine-cardiovascular-and-behavioral-responses-to-stress
#15
Annette D de Kloet, Lei Wang, Soledad Pitra, Helmut Hiller, Justin A Smith, Yalun Tan, Dani Nguyen, Karlena M Cahill, Colin Sumners, Javier E Stern, Eric G Krause
Stress elicits neuroendocrine, autonomic and behavioral responses that mitigate homeostatic imbalance and ensure survival; however, chronic engagement of such responses promotes psychological, cardiovascular and metabolic impairments. Over recent years, the renin-angiotensin system has emerged as a key mediator of stress responding and its related pathologies, but the neuronal circuits that orchestrate these interactions are not known. These studies combine the use of the Cre-recombinase/loxP system in mice with optogenetics to structurally and functionally characterize angiotensin type-1a receptor-containing neurons of the paraventricular nucleus of the hypothalamus, the goal being to determine the extent of their involvement in the regulation of stress responses...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28196404/a-p57-conditional-mutant-allele-that-allows-tracking-of-p57-expressing-cells
#16
Despoina Mademtzoglou, Sonia Alonso-Martin, Ted Hung-Tse Chang, Keren Bismuth, Bernadette Drayton-Libotte, Frédéric Aurade, Frédéric Relaix
p57(Kip2) (p57) is a maternally expressed imprinted gene regulating growth arrest which belongs to the CIP/KIP family of Cyclin-Dependent Kinase Inhibitors. While initially identified as a cell cycle arrest protein through inhibition of cyclin and cyclin-dependent kinase complexes, p57 activity has also been linked to differentiation, apoptosis, and senescence. In addition, p57 has recently been shown to be involved in tumorigenesis and cell fate decisions in stem cells. Yet, p57 function in adult tissues remains poorly characterized due to the perinatal lethality of p57 knock-out mice...
February 14, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28193895/p53-regulates-the-cardiac-transcriptome
#17
Tak W Mak, Ludger Hauck, Daniela Grothe, Filio Billia
The tumor suppressor Trp53 (p53) inhibits cell growth after acute stress by regulating gene transcription. The mammalian genome contains hundreds of p53-binding sites. However, whether p53 participates in the regulation of cardiac tissue homeostasis under normal conditions is not known. To examine the physiologic role of p53 in adult cardiomyocytes in vivo, Cre-loxP-mediated conditional gene targeting in adult mice was used. Genome-wide transcriptome analyses of conditional heart-specific p53 knockout mice were performed...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193684/an-agonist-of-the-protective-factor-sirt1-improves-functional-recovery-and-promotes-neuronal-survival-by-attenuating-inflammation-after-spinal-cord-injury
#18
Haihong Chen, Hao Ji, Ming Zhang, Zude Liu, Lifeng Lao, Chao Deng, Jianwei Chen, Guibin Zhong
Targeting posttraumatic inflammation is crucial for improving locomotor function. SIRT1 has been shown to play a critical role in disease processes such as hepatic inflammation, rheumatoid arthritis and acute lung inflammation by regulating inflammation. However, the role of SIRT1 in spinal cord injury (SCI) is unknown. We hypothesized that SIRT1 plays an important role in improving locomotor function after SCI by regulating neuroinflammation. In this study, we investigated the effect of SIRT1 in SCI using pharmacological intervention (SRT1720) and the Mx1-Cre/loxP recombination system to knock out target genes...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28191637/mammary-alveolar-epithelial-cells-convert-to-brown-adipocytes-in-post-lactating-mice
#19
Antonio Giordano, Jessica Perugini, David M Kristensen, Loris Sartini, Andrea Frontini, Shingo Kajimura, Karsten Kristiansen, Saverio Cinti
During pregnancy and lactation, subcutaneous white adipocytes in the mouse mammary gland transdifferentiate reversibly to milk-secreting epithelial cells. In this study, we demonstrate by transmission electron microscopy that in the post-lactating mammary gland interscapular multilocular adipocytes found close to the mammary alveoli contain milk protein granules. Use of the Cre-loxP recombination system allowed showing that the involuting mammary gland of whey acidic protein-Cre/R26R mice, whose secretory alveolar cells express the lacZ gene during pregnancy, contains some X-Gal-stained and uncoupling protein 1-positive interscapular multilocular adipocytes...
February 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28182872/enhanced-critical-size-calvarial-bone-healing-by-ascs-engineered-with-cre-loxp-based-hybrid-baculovirus
#20
Shih-Chun Lo, Kuei-Chang Li, Yu-Han Chang, Mu-Nung Hsu, Li-Yu Sung, Truong Anh Vu, Yu-Chen Hu
Calvarial bone repair remains challenging for adults. Although adipose-derived stem cells (ASCs) hold promise to heal bone defects, use of ASCs for critical-size calvarial bone repair is ineffective. Stromal cell-derived factor 1 (SDF-1) is a chemokine capable of triggering stem cell migration. Although recombinant SDF-1 protein is co-delivered with other molecules including BMP-2 to facilitate calvarial bone repair, these approaches did not yield satisfactory healing. This study aimed to exploit a newly developed Cre/loxP-based hybrid baculovirus for efficient gene delivery and prolonged transgene expression in ASCs...
January 30, 2017: Biomaterials
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