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https://www.readbyqxmd.com/read/28646022/nf1-hematopoietic-cells-accelerate-malignant-peripheral-nerve-sheath-tumor-development-without-altering-chemotherapy-response
#1
Rebecca D Dodd, Chang-Lung Lee, Tess Overton, Wesley Huang, William C Eward, Lixia Luo, Yan Ma, Davis R Ingram, Keila E Torres, Diana M Cardona, Alexander Lazar, David G Kirsch
Haploinsufficiency in the tumor suppressor NF1 contributes to the pathobiology of type 1 neurofibromatosis, but a related role has not been established in malignant peripheral nerve sheath tumors (MPNST) where NF1 mutations also occur. Patients with NF1-associated MPNST appear to have worse outcomes than patients with sporadic MPNST, but the mechanism underlying this correlation is not understood. To define the impact of stromal genetics on the biology of this malignancy, we developed unique mouse models that reflect the genetics of patient-associated MPNST...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28642969/diverse-metabolic-effects-of-o-glcnacylation-in-the-pancreas-but-limited-effects-in-insulin-sensitive-organs-in-mice
#2
Shogo Ida, Katsutaro Morino, Osamu Sekine, Natsuko Ohashi, Shinji Kume, Tokuhiro Chano, Kanako Iwasaki, Norio Harada, Nobuya Inagaki, Satoshi Ugi, Hiroshi Maegawa
AIMS/HYPOTHESIS: O-GlcNAcylation is characterised by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (OGT) and serves in sensing intracellular nutrients by modulating various cellular processes. Although it has been speculated that O-GlcNAcylation is associated with glucose metabolism, its exact role in whole body glucose metabolism has not been fully elucidated. Here, we investigated whether loss of O-GlcNAcylation globally and in specific organs affected glucose metabolism in mammals under physiological conditions...
June 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28637242/yap-and-wwtr1-regulate-the-expression-of-sex-determining-genes-in-sertoli-cells-but-their-inactivation-does-not-cause-sex-reversal
#3
Adrien Levasseur, Marilène Paquet, Derek Boerboom, Alexandre Boyer
Yes-associated protein (YAP) and WW containing transcription regulator 1 (WWTR1) are two functionally redundant transcriptional regulators that are downstream effectors of the Hippo signaling pathway, and that act as major regulators of cell growth and differentiation. To elucidate their role in Sertoli cells, primary Sertoli cell culture from Yapflox/flox; Wwtr1flox/flox animals were infected with a Cre recombinase-expressing adenovirus. Concomitant inactivation of Yap and Wwtr1 resulted in a decrease in the mRNA levels of the male sex differentiation genes Dhh, Dmrt1, Sox9 and Wt1, whereas those of genes involved in female differentiation (Wnt4, Rspo1 and Foxl2) were induced...
June 16, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28626064/monitoring-c3ar-expression-using-a-floxed-tdtomato-c3ar-reporter-knock-in-mouse
#4
Katharina M Quell, Christian M Karsten, Anna Kordowski, Larissa Nogueira Almeida, Daria Briukhovetska, Anna V Wiese, Jing Sun, Fanny Ender, Konstantina Antoniou, Torsten Schröder, Inken Schmudde, Johann L Berger, Peter König, Tillman Vollbrandt, Yves Laumonnier, Jörg Köhl
C3a exerts multiple biologic functions through activation of its cognate C3a receptor. C3(-/-) and C3aR(-/-) mice have been instrumental in defining important roles of the C3a/C3aR axis in the regulation of acute and chronic inflammatory diseases, including ischemia/reperfusion injury, allergic asthma, autoimmune nephritis, and rheumatoid arthritis. Surprisingly little is known about C3aR expression and function in immune and stromal cells. To close this gap, we generated a floxed tandem-dye Tomato (tdTomato)-C3aR reporter knock-in mouse, which we used to monitor C3aR expression in cells residing in the lung, airways, lamina propria (LP) of the small intestine, brain, visceral adipose tissue, bone marrow (BM), spleen, and the circulation...
June 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28621199/sciatic-nerve-regeneration-by-transplantation-of-in-vitro-differentiated-nucleus-pulposus-progenitor-cells
#5
Takayuki Ishii, Daisuke Sakai, Jordy Schol, Tomoko Nakai, Kaori Suyama, Masahiko Watanabe
AIM: To assess the applicability of mouse intervertebral disc-derived nucleus pulposus (NP) progenitor cells as a cell source for sciatic nerve regeneration. MATERIALS & METHODS: P0-Cre/Floxed-EGFP-transgenic mouse-derived NP progenitor cells were differentiated to Schwann-like cells in conventional induction medium. Schwann-like cells were subsequently transplanted into a mouse model of sciatic nerve transection, and nerve regeneration assessed by immunohistochemistry, electron microscopy and functional walking track analysis and heat stimulus reflex...
June 16, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28620387/notch-regulates-macrophage-mediated-inflammation-in-diabetic-wound-healing
#6
Andrew S Kimball, Amrita D Joshi, Anna E Boniakowski, Matthew Schaller, Jooho Chung, Ronald Allen, Jennifer Bermick, William F Carson, Peter K Henke, Ivan Maillard, Steve L Kunkel, Katherine A Gallagher
Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAML(floxed)Lyz2(Cre+) ) demonstrated delayed early healing (days 1-3) and wound macrophages had decreased inflammatory gene expression...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28620244/specific-ablation-of-mouse-fam20c-in-cells-expressing-type-i-collagen-leads-to-skeletal-defects-and-hypophosphatemia
#7
Peihong Liu, Su Ma, Hua Zhang, Chao Liu, Yongbo Lu, Li Chen, Chunlin Qin
FAM20C mutations in humans cause Raine syndrome and our previous studies showed that global inactivation of mouse Fam20C led to bone and dental defects. By crossbreeding 2.3  kb Col 1a1-Cre mice with Fam20C (flox/flox) mice, we created 2.3  kb Col 1a1-Cre;Fam20C (foxl/flox) (cKO) mice, in which Fam20C was inactivated in cells expressing Type I collagen. This study showed that the long bones of cKO mice were shorter and had a lower level of mineralization compared to the normal mice. The collagen fibrils in Fam20C-deficient bone were disorganized and thicker while the growth plate cartilage in cKO mice was disorganized and wider compared to the normal mice...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620068/x-box-binding-protein-1-dependent-plasma-cell-responses-limit-the-development-of-atherosclerosis
#8
Andrew P Sage, Meritxell Nus, Jayashree Bagchi Chakraborty, Dimitrios Tsiantoulas, Stephen A Newland, Alison J Finigan, Leanne Masters, Christoph J Binder, Ziad Mallat
Rationale: Diverse B cell responses and functions may be involved in atherosclerosis. Protective antibody responses, such as those against oxidized lipid epitopes, are thought to mainly derive from T cell-independent innate B cell subsets. In contrast, both pathogenic and protective roles have been associated with T cell-dependent antibodies and their importance in both humans and mouse models is still unclear. Objective: To specifically target antibody production by plasma cells and determine the impact on atherosclerotic plaque development in mice with and without CD4+ T cells...
June 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28615301/irf4-dependent-cd103-cd11b-dendritic-cells-and-the-intestinal-microbiome-regulate-monocyte-and-macrophage-activation-and-intestinal-peristalsis-in-postoperative-ileus
#9
Judith-Mira Pohl, Sebastian Gutweiler, Stephanie Thiebes, Julia K Volke, Ludger Klein-Hitpass, Denise Zwanziger, Matthias Gunzer, Steffen Jung, William W Agace, Daniel Robert Engel, Christian Kurts
OBJECTIVE: Postoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. Here, we have investigated the mechanism that activates these cells and the contribution of the intestinal microbiota for POI induction. DESIGN: POI was induced by manipulating the intestine of mice, which selectively lack DCs, monocytes or macrophages. The disease severity in the small and large intestine was analysed by determining the distribution of orally applied fluorescein isothiocyanate-dextran and by measuring the excretion time of a retrogradely inserted glass ball...
June 14, 2017: Gut
https://www.readbyqxmd.com/read/28611114/notch1-deficiency-in-postnatal-neural-progenitor-cells-in-the-dentate-gyrus-leads-to-emotional-and-cognitive-impairment
#10
Shufang Feng, Tianyao Shi, Jiangxia Qiu, Haihong Yang, Yan Wu, Wenxia Zhou, Wei Wang, Haitao Wu
It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in hippocampal mature neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus...
June 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28608929/high-grade-serous-carcinomas-arise-in-the-mouse-oviduct-via-defects-linked-to-the-human-disease
#11
Yali Zhai, Rong Wu, Rork Kuick, Michael S Sessine, Stephanie Schulman, Megan Green, Eric R Fearon, Kathleen R Cho
Recent studies suggest that the most common and lethal type of "ovarian" cancer, high-grade serous carcinoma (HGSC), usually arises from epithelium on the fallopian tube fimbriae, and not from the ovarian surface epithelium (OSE). We have developed Ovgp1-iCreER(T2) mice in which the Ovgp1 promoter controls expression of tamoxifen (TAM)-regulated Cre recombinase in oviductal epithelium - the murine equivalent of human fallopian tube epithelium (FTE). We employed Ovgp1-iCreER(T2) mice to show that FTE-specific inactivation of several different combinations of tumour suppressor genes recurrently mutated in human HGSCs - namely Brca1, Trp53, Rb1, and Nf1 - results in serous tubal intraepithelial carcinomas (STICs) that progress to HGSC or carcinosarcoma, and to widely metastatic disease in a subset of mice...
June 13, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28607127/role-of-the-primary-cilia-on-the-macula-densa-and-thick-ascending-limbs-in-regulation-of-sodium-excretion-and-hemodynamics
#12
Jiangping Song, Lei Wang, Fan Fan, Jin Wei, Jie Zhang, Yan Lu, Yiling Fu, Shaohui Wang, Luis A Juncos, Ruisheng Liu
We investigated the significance of the primary cilia on the macula densa and thick ascending limb (TAL) in regulation of renal hemodynamics, sodium excretion, and blood pressure in this study. A tissue-specific primary cilia knock-out (KO) mouse line was generated by crossing NKCC2-Cre mice with IFT88-Δ/flox mice (NKCC2(CRE); IFT88Δ(/flox)), in which the primary cilia were deleted from the macula densa and TAL. NO generation was measured with a fluorescent dye (4,5-diaminofluorescein diacetate) in isolated perfused juxtaglomerular apparatus...
June 12, 2017: Hypertension
https://www.readbyqxmd.com/read/28602064/notch-signaling-in-the-collecting-duct-regulates-renal-tubulointerstitial-fibrosis-induced-by-unilateral-ureteral-obstruction-in-mice
#13
Arum Choi, Sun Ah Nam, Wan-Young Kim, Sang Hee Park, Hyang Kim, Chul Woo Yang, Jin Kim, Yong Kyun Kim
Background/Aims: Mind bomb-1 (Mib1) encodes an E3 ubiquitin ligase, which is required for the initiation of Notch signaling. Recently, it was demonstrated that the renal collecting duct plays an important role in renal fibrosis. Here, we investigated the role of Notch signaling in renal fibrosis using conditional knockout mice with the specific ablation of Mib1 in renal collecting duct principal cells. Methods: Mib1-floxed mice (Mib1f/f) were crossed with aquaporin 2 (AQP2)-Cre mice in order to generate principal cell-specific Mib1 knockout mice (Mib1f/f :AQP2-Cre+)...
May 26, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28600811/inducible-knockdown-of-pregnancy-associated-plasma-protein-a-gene-expression-in-adult-female-mice-extends-life-span
#14
Laurie K Bale, Sally A West, Cheryl A Conover
Pregnancy-associated plasma protein-A (PAPP-A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild-type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP-A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)-inducible Cre recombinase-mediated excision of the floxed PAPP-A (fPAPP-A) gene in mice at 5 months of age. fPAPP-A mice, which were either positive (pos) or negative (neg) for Tam-Cre, received Tam treatment with quarterly boosters...
June 9, 2017: Aging Cell
https://www.readbyqxmd.com/read/28596376/cre-lox-studies-identify-resident-macrophages-as-the-major-source-of-circulating-coagulation-factor-xiii-a
#15
Cora M L Beckers, Kingsley R Simpson, Kathryn J Griffin, Jane M Brown, Lih T Cheah, Kerrie A Smith, Jean Vacher, Paul A Cordell, Mark T Kearney, Peter J Grant, Richard J Pease
OBJECTIVE: To establish the cellular source of plasma factor (F)XIII-A. APPROACH AND RESULTS: A novel mouse floxed for the F13a1 gene, FXIII-A(flox/flox) (Flox), was crossed with myeloid- and platelet-cre-expressing mice, and cellular FXIII-A mRNA expression and plasma and platelet FXIII-A levels were measured. The platelet factor 4-cre.Flox cross abolished platelet FXIII-A and reduced plasma FXIII-A to 23±3% (P<0.001). However, the effect of platelet factor 4-cre on plasma FXIII-A was exerted outside of the megakaryocyte lineage because plasma FXIII-A was not reduced in the Mpl(-/-) mouse, despite marked thrombocytopenia...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28581520/klf10-loss-in-the-pancreas-provokes-activation-of-sdf-1-and-induces-distant-metastases-of-pancreatic-ductal-adenocarcinoma-in-the-kras-g12d-p53-flox-flox-model
#16
C-C Weng, J R Hawse, M Subramaniam, V H S Chang, W C Y Yu, W-C Hung, L-T Chen, K-H Cheng
Krüppel-like transcription factor 10 (KLF10), also named as TIEG1, plays essential roles in mediating transforming growth factor beta (TGFβ) signaling and has been shown to function as a tumor suppressor in multiple cancer types. However, its roles in mediating cancer progression in vivo have yet to be fully characterized. Here, we have employed two well-characterized Pdx-1CreLSL-Kras(G12D) and Pdx-1CreLSL-Kras(G12D)p53(L/L) pancreatic cancer models to ablate KLF10 expression and determine the impact of KLF10 deletion on tumor development and progression...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28569793/oocyte-specific-deletion-of-furin-leads-to-female-infertility-by-causing-early-secondary-follicle-arrest-in-mice
#17
Tie-Gang Meng, Meng-Wen Hu, Xue-Shan Ma, Lin Huang, Qiu-Xia Liang, Yue Yuan, Yi Hou, Hongmei Wang, Heide Schatten, Zhen-Bo Wang, Qing-Yuan Sun
The process of follicular development involves communications between oocyte and surrounding granulosa cells. FURIN is a member of the family of proprotein convertases that is involved in the activation of a large number of zymogens and proproteins by cleavage at its recognition motif. To investigate the functions of FURIN in female fertility, furin(flox/flox) (fur(fl/fl)) mice were crossed with Zp3-Cre mice and Gdf9-Cre, respectively, to achieve oocyte-specific disruption of FURIN. Here we report for the first time that FURIN is dispensable for primordial follicle maintenance and activation but important for early secondary follicular development, as ablation of FURIN in oocytes caused failure of follicle development beyond the type 4 and/or 5a follicles in mutant mice, resulting in increased number of early secondary follicles and the severely decreased number of mature follicles, thus anovulation and infertility...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28569405/sex-dependent-osteoblast-stage-specific-effects-of-progesterone-receptor-on-bone-acquisition
#18
Zhendong A Zhong, Alexander Kot, Yu-An E Lay, Hongliang Zhang, Junjing Jia, Nancy E Lane, Wei Yao
The role of the progesterone receptor (PR) in the regulation of sexual dimorphism in bone has yet to be determined. Here we utilized genetic fate mapping and western blotting to demonstrate age-dependent PR expression in the mouse femoral metaphysis and diaphysis. To define sex-dependent and osteoblast stage-specific effects of PR on bone acquisition, we selectively deleted PR at different stages of osteoblast differentiation. We found that when Prx1-Cre mice were crossed with PR floxed mice to generate a MSC conditional KO model (Prx1; PRcKO), the mutant mice developed greater trabecular bone volume with higher mineral apposition rate and bone formation...
June 1, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28561373/c-jun-n-terminal-kinases-jnks-are-critical-mediators-of-osteoblast-activity-in-vivo
#19
Ren Xu, Chao Zhang, Dong Yeon Shin, Jung-Min Kim, Sarfaraz Lalani, Na Li, Yeon-Suk Yang, Yifang Liu, Mark Eiseman, Roger J Davis, Jae-Hyuck Shim, Matthew B Greenblatt
The c-Jun N-terminal kinases (JNKs) are ancient and evolutionarily conserved regulators of proliferation, differentiation and cell death responses. Currently, in vitro studies offer conflicting data about whether the JNK pathway augments or represses osteoblast differentiation, and the contribution of the JNK pathway to regulation of bone mass in vivo remains unclear. Here we show that Jnk1(-/-) mice display severe osteopenia due to impaired bone formation, whereas Jnk2(-/-) mice display a mild osteopenia only evident in long bones...
May 31, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28552963/bim-expression-in-endothelial-cells-and-pericytes-is-essential-for-regression-of-the-fetal-ocular-vasculature
#20
Shoujian Wang, Ismail S Zaitoun, Ryan P Johnson, Nasim Jamali, Zafer Gurel, Catherine M Wintheiser, Andreas Strasser, Volkhard Lindner, Nader Sheibani, Christine M Sorenson
Apoptosis plays a central role in developmental and pathological angiogenesis and vessel regression. Bim is a pro-apoptotic Bcl-2 family member that plays a prominent role in both developmental and pathological ocular vessel regression, and neovascularization. Endothelial cells (EC) and pericytes (PC) each play unique roles during vascular development, maintenance and regression. We recently showed that germline deletion of Bim results in persistent hyaloid vasculature, increased retinal vascular density and prevents retinal vessel regression in response to hyperoxia...
2017: PloS One
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