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https://www.readbyqxmd.com/read/28938604/inflammation-and-stem-markers-association-to-pim1-pim2-kinase-induced-tumors-in-breast-and-uterus
#1
Manuel-Pedro Jiménez-García, Antonio Lucena-Cacace, María-José Robles-Frías, Irene Ferrer, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938492/a-long-noncoding-rna-lncrna-amhr2-plays-a-role-in-amhr2-gene-activation-in-mouse-ovarian-granulosa-cells
#2
Atsushi P Kimura, Ryoma Yoneda, Misuzu Kurihara, Shota Mayama, Shin Matsubara
Anti-Müllerian hormone (AMH) is critical to the regression of Müllerian ducts during mammalian male differentiation and targets ovarian granulosa cells and testicular Sertoli and Leydig cells of adults. Specific effects of AMH are exerted via its receptor, AMH type II receptor (Amhr2), but the mechanism by which the Amhr2 gene is specifically activated is not fully understood. To see whether a proximal promoter was sufficient to Amhr2 gene activation, we generated transgenic mice that bore the enhanced green fluorescent protein (EGFP) gene driven by a 500-bp mouse Amhr2 gene promoter...
September 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938491/inhibition-of-fgfr-signaling-partially-rescues-hypophosphatemic-rickets-in-hmwfgf2-tg-male-mice
#3
Liping Xiao, Erxia Du, Collin Homer-Bouthiette, Marja M Hurley
Transgenic mice harboring high molecular weight FGF2 isoforms (HMWTg) in osteoblast lineage cells phenocopy human X-linked hypophosphatemic rickets (XLH) and Hyp murine model of XLH demonstrating increased FGF23/FGF receptor signaling and hypophosphatemic rickets. Since HMWFGF2 was upregulated in bones of Hyp mice and abnormal FGF receptor (FGFR) signaling is important in XLH, HMWTg mice were used to examine the effect of the FGFR inhibitor NVP-BGJ398, now in clinical trials for cancer therapy, on hypophosphatemic rickets...
August 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938453/variable-effects-of-dietary-selenium-in-mice-that-spontaneously-develop-a-spectrum-of-thyroid-autoantibodies
#4
Sandra M McLachlan, Holly Aliesky, Bianca Banuelos, Shane S Que Hee, Basil Rapoport
Selenium (Se) is a critical element in thyroid function and variable dietary Se intake influences immunity. Consequently, dietary Se could influence development of thyroid autoimmunity and provide an adjunct to treat autoimmune thyroid dysfunction. NOD.H2h4 mice spontaneously develop autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO). This mouse strain expressing a human TSHR A-subunit transgene in the thyroid also develops pathogenic TSHR autoantibodies. In this report, we investigated whether dietary Se influences these immune processes...
August 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938414/sex-and-tissue-specific-role-of-estrogen-sulfotransferase-in-energy-homeostasis-and-insulin-sensitivity
#5
Wojciech G Garbacz, Mengxi Jiang, Meishu Xu, Jun Yamauchi, H Henry Dong, Wen Xie
Estrogen Sulfotransferase (EST) catalyzes the sulfoconjugation and deactivation of estrogens. Previously we showed that loss of Est in male ob/ob mice, but not in female ob/ob mice, exacerbated the diabetic phenotype, but the underlying mechanism was unclear. Here we show that transgenic reconstitution of Est in the adipose tissue, but not in the liver, attenuated diabetic phenotype in Est deficient ob/ob mice (obe). Mechanistically, adipose reconstitution of Est in obe mice (oae) resulted in reduced local and systemic inflammation, improved insulin sensitivity, and increased energy expenditure...
September 5, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938396/transgenic-expression-of-the-vitamin-d-receptor-restricted-to-the-ileum-cecum-and-colon-of-vitamin-d-receptor-knockout-mice-rescues-vitamin-d-receptor-dependent-rickets
#6
Puneet Dhawan, Vaishali Veldurthy, Ghassan Yehia, Connie Hsaio, Angela Porta, Ki-In Kim, Nishant Patel, Liesbet Lieben, Lieve Verlinden, Geert Carmeliet, Sylvia Christakos
Although the intestine plays the major role in 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) action on calcium homeostasis, the mechanisms involved remain incompletely understood. The established model of 1,25(OH)2D3 regulated intestinal calcium absorption postulates a critical role for the duodenum. However it is the distal intestine where 70 -80% of the ingested calcium is absorbed. In order to test directly the role of 1,25(OH)2D3 and the vitamin D receptor (VDR) in the distal intestine, 3 independent knockout (KO) /transgenic (TG) lines expressing VDR exclusively in the ileum, cecum and colon were generated by breeding VDR KO mice with TG mice expressing human (h)VDR under the control of the 9...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28935984/regulation-of-axonal-regeneration-by-the-level-of-function-of-the-endogenous-nogo-receptor-antagonist-lotus
#7
Tomoko Hirokawa, Yixiao Zou, Yuji Kurihara, Zhaoxin Jiang, Yusuke Sakakibara, Hiromu Ito, Kengo Funakoshi, Nobutaka Kawahara, Yoshio Goshima, Stephen M Strittmatter, Kohtaro Takei
Axonal regeneration in the adult mammalian central nervous system is limited in part by the non-permissive environment, including axonal growth inhibitors such as the Nogo-A protein. How the functions of these inhibitors can be blocked remains unclear. Here, we examined the role of LOTUS, an endogenous Nogo receptor antagonist, in promoting functional recovery and neural repair after spinal cord injury (SCI), as well as axonal regeneration after optic nerve crush. Wild-type untreated mice show incomplete but substantial intrinsic motor recovery after SCI...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935977/zebrafish-in-vivo-screening-for-compounds-amplifying-hematopoietic-stem-and-progenitor-cells-preclinical-validation-in-human-cd34-stem-and-progenitor-cells
#8
Guruchandar Arulmozhivarman, Martin Kräter, Manja Wobus, Jens Friedrichs, Elham Pishali Bejestani, Katrin Müller, Katrin Lambert, Dimitra Alexopoulou, Andreas Dahl, Martin Stöter, Marc Bickle, Nona Shayegi, Jochen Hampe, Friedrich Stölzel, Michael Brand, Malte von Bonin, Martin Bornhäuser
The identification of small molecules that either increase the number and/or enhance the activity of human hematopoietic stem and progenitor cells (hHSPCs) during ex vivo expansion remains challenging. We used an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model and identified histone deacetylase inhibitors (HDACIs), particularly valproic acid (VPA), as significant enhancers of the number of phenotypic HSPCs, both in vivo and during ex vivo expansion. The long-term functionality of these expanded hHSPCs was verified in a xenotransplantation model with NSG mice...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935759/lymphangiogenesis-facilitates-initial-lymph-formation-and-enhances-the-dendritic-cell-mobilizing-chemokine-ccl21-without-affecting-migration
#9
Tine V Karlsen, Tore Reikvam, Anne Tofteberg, Elham Nikpey, Trude Skogstrand, Marek Wagner, Olav Tenstad, Helge Wiig
OBJECTIVE: Lymphatic vessels play an important role in body fluid, as well as immune system homeostasis. Although the role of malfunctioning or missing lymphatics has been studied extensively, less is known on the functional consequences of a chronically expanded lymphatic network or lymphangiogenesis. APPROACH AND RESULTS: To this end, we used K14-VEGF-C (keratin-14 vascular endothelial growth factor-C) transgenic mice overexpressing the vascular endothelial growth factor C in skin and investigated the responses to inflammatory and fluid volume challenges...
September 21, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28935639/isolation-and-characterization-of-endothelial-to-mesenchymal-transition-cells-in-pulmonary-arterial-hypertension
#10
Toshio Suzuki, Erica J Carrier, Megha A Talati, Anandharajan Rathinasabapathy, Xinping Chen, Rintaro Nishimura, Yuji Tada, Koichiro Tatsumi, James D West
Endothelial-to-mesenchymal transition (EndMT) is a process in which endothelial cells lose polarity and cell-to-cell contacts, and undergo a dramatic remodeling of the cytoskeleton. It has been implicated in initiation and progression of pulmonary arterial hypertension (PAH). However, the characteristics of cells which have undergone EndMT-cells in vivo have not been reported and so remain unclear. To study this, sugen5416 and hypoxia (SuHx)-induced PAH was established in Cdh5-Cre / Gt(ROSA)26Sor(tm4(ACTB-tdTomato,-EGFP)Luo)/J double-transgenic mice, in which GFP was stably expressed in pan-endothelial cells...
September 21, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28935572/macrophage-infiltration-is-a-causative-factor-for-ligamentum-flavum-hypertrophy-through-the-activation-of-collagen-production-in-fibroblasts
#11
Takeyuki Saito, Masamitsu Hara, Hiromi Kumamaru, Kazu Kobayakawa, Kazuya Yokota, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yoshihiro Matsumoto, Kenichi Kawaguchi, Mitsumasa Hayashida, Yutaka Inagaki, Keiichiro Shiba, Yasuharu Nakashima, Seiji Okada
Ligamentum flavum (LF) hypertrophy causes lumbar spinal canal stenosis, leading to leg pain and disability in activities of daily living in elderly individuals. Although there have been previous studies on LF hypertrophy, its pathomechanisms have not been fully elucidated. In this study, we demonstrated that infiltrating macrophages were a causative factor for LF hypertrophy. Induction of macrophages into the mouse LF by applying a micro-injury resulted in LF hypertrophy along with collagen accumulation and fibroblasts proliferation at the injured site, which were very similar to the characteristics observed in the severely hypertrophied LF of human...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28935569/constitutive-cd40-signaling-in-dendritic-cells-limits-atherosclerosis-by-provoking-inflammatory-bowel-disease-and-ensuing-cholesterol-malabsorption
#12
Pascal Kusters, Tom Seijkens, Christina Bürger, Bart Legein, Holger Winkels, Marion Gijbels, Christian Barthels, Remy Bennett, Linda Beckers, Dorothee Atzler, Erik Biessen, Thomas Brocker, Christian Weber, Norbert Gerdes, Esther Lutgens
The co-stimulatory molecule CD40 is a major driver of atherosclerosis. It is expressed on a wide variety of cell types including mature dendritic cells (DCs) and is required for optimal T cell activation and expansion. It remains undetermined if and how CD40 on DCs impacts the pathogenesis of atherosclerosis. Here we examined the effects of constitutively active CD40 in DCs on atherosclerosis, using low-density lipoprotein-deficient (Ldlr(-/-)) bone-marrow chimeras that express a transgene containing an engineered latent membrane protein 1 (LMP)/CD40 fusion protein conferring constitutive CD40 signaling under control of the DC-specific CD11c promoter (DC-LMP1/CD40)...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28935002/spontaneous-development-of-cutaneous-squamous-cell-carcinoma-in-mice-with-cell-specific-deletion-of-inhibitor-of-%C3%AE%C2%BAb-kinase-2
#13
Kelly S Kirkley, Kelly D Walton, Colleen Duncan, Ronald B Tjalkens
The deletion of NFκB in epithelial tissues by using skin-specific promoters can cause both tumor formation and severe inflammatory dermatitis, indicating that this signaling pathway is important for the maintenance of immune homeostasis in epithelial tissues. In the present study, we crossed mice transgenic for loxP-Ikbk2 and human Gfap-cre to selectively delete IKK2 in CNS astrocytes. Unexpectedly, a subset of mice developed severe and progressive skin lesions marked by hyperplasia, hyperkeratosis, dysplasia, inflammation, and neoplasia with a subset of lesions diagnosed as squamous cell carcinoma (SCC)...
October 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28934472/controlled-re-activation-of-epigenetically-silenced-tet-promoter-driven-transgene-expression-by-targeted-demethylation
#14
Natascha Gödecke, Lisha Zha, Shawal Spencer, Sara Behme, Pamela Riemer, Michael Rehli, Hansjörg Hauser, Dagmar Wirth
Faithful expression of transgenes in cell cultures and mice is often challenged by locus dependent epigenetic silencing. We investigated silencing of Tet-controlled expression cassettes within the mouse ROSA26 locus. We observed pronounced DNA methylation of the Tet promoter concomitant with loss of expression in mES cells as well as in differentiated cells and transgenic animals. Strikingly, the ROSA26 promoter remains active and methylation free indicating that this silencing mechanism specifically affects the transgene, but does not spread to the host's chromosomal neighborhood...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934394/microrna-455-3p-as-a-potential-peripheral-biomarker-for-alzheimer-s-disease
#15
Subodh Kumar, Murali Vijayan, P Hemachandra Reddy
The purpose of our study was to identify microRNAs (miRNAs) as early detectable peripheral biomarkers in Alzheimer's disease (AD). To achieve our objective, we assessed miRNAs in serum samples from AD patients and Mild cognitive impairment (MCI) subjects relative to healthy controls. We used Affymetrix microarray analysis and validated differentially expressed miRNAs using qRT-PCR. We further validated miRNA data using AD postmortem brains, amyloid precursor protein transgenic mice and AD cell lines. We identified a gradual upregulation of four miRNAs: miR-455-3p, miR-4668-5p, miR-3613-3p and miR-4674...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934383/overexpression-of-micrornas-from-the-gtl2-rian-locus-contributes-to-postnatal-death-in-mice
#16
Soichiro Kumamoto, Nozomi Takahashi, Kayo Nomura, Makoto Fujiwara, Megumi Kijioka, Yoshinobu Uno, Yoichi Matsuda, Yusuke Sotomaru, Tomohiro Kono
The Dlk1-Dio3 imprinted domain functions in embryonic development but the roles of noncoding RNAs expressed from this domain remain unclear. We addressed this question by generating transgenic (TG) mice harbouring a BAC carrying IG-DMR (intergenic-differentially methylated region), Gtl2-DMR, Gtl2, Rtl1/Rtl1as, and part of Rian. High postnatal lethality (>85%) of the BAC-TG pups was observed in the maternally transmitted individuals (MAT-TG), but not following paternal transmission (PAT-TG). The DNA methylation status of IG-DMR and Gtl2-DMR in the BAC-allele was paternally imprinted similar to the genomic allele...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934252/three-way-interaction-model-to-trace-the-mechanisms-involved-in-alzheimer-s-disease-transgenic-mice
#17
Nasibeh Khayer, Sayed-Amir Marashi, Mehdi Mirzaie, Fatemeh Goshadrou
Alzheimer's disease (AD) is the most common cause for dementia in human. Currently, more than 46 million people in the world suffer from AD and it is estimated that by 2050 this number increases to more than 131 million. AD is considered as a complex disease. Therefore, understanding the mechanism of AD is a universal challenge. Nowadays, a huge number of disease-related high-throughput "omics" datasets are freely available. Such datasets contain valuable information about disease-related pathways and their corresponding gene interactions...
2017: PloS One
https://www.readbyqxmd.com/read/28934250/changes-in-striatal-activity-and-functional-connectivity-in-a-mouse-model-of-huntington-s-disease
#18
Magali Cabanas, Fares Bassil, Nicole Mons, Maurice Garret, Yoon H Cho
Hereditary Huntington's disease (HD) is associated with progressive motor, cognitive and psychiatric symptoms. A primary consequence of the HD mutation is the preferential loss of medium spiny projection cells with relative sparing of local interneurons in the striatum. In addition, among GABAergic striatal projection cells, indirect pathway cells expressing D2 dopamine receptors are lost earlier than direct pathway cells expressing D1 receptors. To test in vivo the functional integrity of direct and indirect pathways as well as interneurons in the striatum of male R6/1 transgenic mice, we assessed their c-Fos expression levels induced by a striatal-dependent cognitive task and compared them with age-matched wild-type littermates...
2017: PloS One
https://www.readbyqxmd.com/read/28934241/hla-dr7-and-hla-dq2-transgenic-mouse-strains-tested-as-a-model-system-for-ximelagatran-hepatotoxicity
#19
Hanna Lundgren, Klara Martinsson, Karin Cederbrant, Johan Jirholt, Daniel Mucs, Katja Madeyski-Bengtson, Said Havarinasab, Per Hultman
The oral thrombin inhibitor ximelagatran was withdrawn in the late clinical trial phase because it adversely affected the liver. In approximately 8% of treated patients, drug-induced liver injury (DILI) was expressed as transient alanine transaminase (ALT) elevations. No evidence of DILI had been revealed in the pre-clinical in vivo studies. A whole genome scan study performed on the clinical study material identified a strong genetic association between the major histocompatibility complex alleles for human leucocyte antigens (HLA) (HLA-DR7 and HLA-DQ2) and elevated ALT levels in treated patients...
2017: PloS One
https://www.readbyqxmd.com/read/28933221/neural-stem-cell-transplantation-is-associated-with-inhibition-of-apoptosis-bcl-xl-upregulation-and-recovery-of-neurological-function-in-a-rat-model-of-traumatic-brain-injury
#20
Ai-Lan Pang, Liu-Lin Xiong, Qing-Jie Xia, Fen Liu, You-Cui Wang, Fei Liu, Piao Zhang, Bu-Liang Meng, Sheng Tan, Ting-Hua Wang
Traumatic brain injury (TBI) is a common disease that usually causes severe neurological damage, and current treatment is far from satisfactory. The neuroprotective effects of neural stem cell (NSC) transplantation in the injured nervous system have largely been known, but the underlying mechanisms remain unclear, and their limited sources impede their clinical application. Here, we established a rat model of TBI by dropping a weight onto the cortical motor area of the brain and explored the effect of engrafted NSCs (passage 3, derived from the hippocampus of embryonic 12- to 14-d green fluorescent protein transgenic mice) on TBI rats...
July 2017: Cell Transplantation
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