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https://www.readbyqxmd.com/read/29774544/functional-molecules-in-mesothelial-to-mesenchymal-transition-revealed-by-transcriptome-analyses
#1
Sara Namvar, Adrian S Woolf, Leo A H Zeef, Thomas Wilm, Bettina Wilm, Sarah E Herrick
Peritoneal fibrosis is a common complication of abdominal and pelvic surgery, and can also be triggered by peritoneal dialysis, resulting in treatment failure. In these settings, fibrosis is driven by activated myofibroblasts that are considered to be partly derived by mesothelial-to-mesenchymal transition (MMT). We hypothesised that if the molecular signature of MMT could be better defined, these insights could be exploited to block this pathological cellular transition. Rat peritoneal mesothelial cells were purified, using an antibody to HBME1, a protein present on mesothelial cell microvilli, and streptavidin nanobead technology...
May 17, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29774064/tumour-homing-chimeric-polypeptide-conjugated-polypyrrole-nanoparticles-for-imaging-guided-synergistic-photothermal-and-chemical-therapy-of-cancer
#2
Mengmeng Sun, Jianwen Guo, Hanjun Hao, Tong Tong, Kun Wang, Weiping Gao
Near-infrared (NIR)-absorbing conjugated polymer nanoparticles are interesting for imaging-guided combination therapy, especially for synergistic photothermal therapy and chemotherapy; however, most of them target tumours passively through the enhanced permeability and retention (EPR) effect, leading to low utilization efficiency. To address this problem, we report an active tumour-targeting strategy of tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugated-polymer nanoparticles as a new class of drug nanocarriers for imaging-guided combination therapy of cancer...
2018: Theranostics
https://www.readbyqxmd.com/read/29773907/an-approach-to-monitoring-home-cage-behavior-in-mice-that-facilitates-data-sharing
#3
Edoardo Balzani, Matteo Falappa, Fuat Balcà, Valter Tucci
Genetically modified mice are used as models for a variety of human behavioral conditions. However, behavioral phenotyping can be a major bottleneck in mouse genetics because many of the classic protocols are too long and/or are vulnerable to unaccountable sources of variance, leading to inconsistent results between centers. We developed a home-cage approach using a Chora feeder that is controlled by-and sends data to-software. In this approach, mice are tested in the standard cages in which they are held for husbandry, which removes confounding variables such as the stress induced by out-of-cage testing...
June 2018: Nature Protocols
https://www.readbyqxmd.com/read/29773902/nedd9-promotes-oncogenic-signaling-a-stem-mesenchymal-gene-signature-and-aggressive-ovarian-cancer-growth-in-mice
#4
Rashid Gabbasov, Fang Xiao, Caitlin G Howe, Laura E Bickel, Shane W O'Brien, Daniel Benrubi, Thuy-Vy Do, Yan Zhou, Emmanuelle Nicolas, Kathy Q Cai, Samuel Litwin, Sachiko Seo, Erica A Golemis, Denise C Connolly
Neural precursor cell expressed, developmentally downregulated 9 (NEDD9) supports oncogenic signaling in a number of solid and hematologic tumors. Little is known about the role of NEDD9 in ovarian carcinoma (OC), but available data suggest elevated mRNA and protein expression in advanced stage high-grade cancers. We used a transgenic MISIIR-TAg mouse OC model combined with genetic ablation of Nedd9 to investigate its action in the development and progression of OC. A Nedd9-/- genotype delayed tumor growth rate, reduced incidence of ascites, and reduced expression and activation of signaling proteins including SRC, STAT3, E-cadherin, and AURKA...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29773788/immunogene-therapy-with-fusogenic-nanoparticles-modulates-macrophage-response-to-staphylococcus-aureus
#5
Byungji Kim, Hong-Bo Pang, Jinyoung Kang, Ji-Ho Park, Erkki Ruoslahti, Michael J Sailor
The incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system's response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29772390/pathobiology-of-christianson-syndrome-linking-disrupted-endosomal-lysosomal-function-with-intellectual-disability-and-sensory-impairments
#6
Mallory Kerner-Rossi, Maria Gulinello, Steven Walkley, Kostantin Dobrenis
Christianson syndrome (CS) is a recently described rare neurogenetic disorder presenting early in life with a broad range of neurological symptoms, including severe intellectual disability with nonverbal status, hyperactivity, epilepsy, and progressive ataxia due to cerebellar atrophy. CS is due to loss-of-function mutations in SLC9A6, encoding NHE6, a sodium-hydrogen exchanger involved in the regulation of early endosomal pH. Here we review what is currently known about the neuropathogenesis of CS, based on insights from experimental models, which to date have focused on mechanisms that affect the CNS, specifically the brain...
May 14, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29772389/hippocampal-microglia-modifications-in-c57bl-6-pah-enu2-and-btbr-pah-enu2-phenylketonuria-pku-mice-depend-on-the-genetic-background-irrespective-of-disturbed-sleep-patterns
#7
Els van der Goot, Vibeke M Bruinenberg, Femke M Hormann, Ulrich L M Eisel, Francjan J van Spronsen, Eddy A Van der Zee
Toxic levels of phenylalanine in blood and brain is a characteristic of (untreated) phenylketonuria (PKU), leading to cognitive deficits in PKU mice. In addition, our recent findings showed that PKU mice (as well as PKU patients) have a disturbed sleep/wake cycle. As a consequence, sleep loss may contribute to cognitive deficits in PKU. Sleep loss has been linked to increased activation of microglia in the hippocampus. In this study, we set out to examine morphological features of the microglia population in the hippocampus of the mouse PKU model, using both the C57Bl/6 and the BTBR strain and their wild-type controls (age 5...
May 14, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29771299/at-the-crossroads-of-fate-somatic-cell-lineage-specification-in-the-fetal-gonad
#8
Emmi Rotgers, Anne Jørgensen, Humphrey Hung-Chang Yao
The reproductive endocrine systems are vastly different between male and female. This sexual dimorphism of endocrine milieu originates from sex-specific differentiation of the somatic cells in the gonads during fetal life. The majority of gonadal somatic cells arise from the adrenogonadal primordium. After separation of the adrenal and gonadal primordia, the gonadal somatic cells initiate sex-specific differentiation during gonadal sex determination with the specification of the supporting cell lineages: Sertoli cells in the testis vs...
May 15, 2018: Endocrine Reviews
https://www.readbyqxmd.com/read/29770532/novel-approaches-to-study-coronary-vasculature-development-in-mice
#9
Hana Kolesová, Martin Bartoš, Wan Chin Hsieh, Veronika Olejníčková, David Sedmera
BACKGROUND: Coronary artery development is an intensely studied field. Mice are a popular genetic model for developmental studies, but there is no widely accepted protocol for high-throughput, high-resolution imaging of their developmental and adult coronary artery anatomy. RESULTS: Using tissue clearing protocols and confocal microscopy, we have analyzed embryonic and juvenile mouse hearts in Cx40:GFP knock-in models with a special focus on septal artery development...
May 17, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29769618/inhibitor-of-apoptosis-proteins-iaps-mediate-collagen-type-xi-alpha-1-driven-cisplatin-resistance-in-ovarian-cancer
#10
Miran Rada, Sameera Nallanthighal, Jennifer Cha, Kerry Ryan, Jessica Sage, Catherine Eldred, Maria Ullo, Sandra Orsulic, Dong-Joo Cheon
Although, cisplatin resistance is a major challenge in the treatment of ovarian cancer, the precise mechanisms underlying cisplatin resistance are not fully understood. Collagen type XI alpha 1 (COL11A1), a gene encoding a minor fibrillar collagen of the extracellular matrix, is identified as one of the most upregulated genes in cisplatin-resistant ovarian cancer and recurrent ovarian cancer. However, the exact functions of COL11A1 in cisplatin resistance are unknown. Here we demonstrate that COL11A1 binds to integrin α1β1 and discoidin domain receptor 2 (DDR2) and activates downstream signaling pathways to inhibit cisplatin-induced apoptosis in ovarian cancer cells...
May 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29769603/components-of-a-new-gene-family-of-ferroxidases-involved-in-virulence-are-functionally-specialized-in-fungal-dimorphism
#11
María Isabel Navarro-Mendoza, Carlos Pérez-Arques, Laura Murcia, Pablo Martínez-García, Carlos Lax, Marta Sanchis, Javier Capilla, Francisco E Nicolás, Victoriano Garre
Mucormycosis is an emerging angio-invasive infection caused by Mucorales that presents unacceptable mortality rates. Iron uptake has been related to mucormycosis, since serum iron availability predisposes the host to suffer this infection. In addition, iron uptake has been described as a limiting factor that determines virulence in other fungal infections, becoming a promising field to study virulence in Mucorales. Here, we identified a gene family of three ferroxidases in Mucor circinelloides, fet3a, fet3b and fet3c, which are overexpressed during infection in a mouse model for mucormycosis, and their expression in vitro is regulated by the availability of iron in the culture media and the dimorphic state...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768727/a-congenic-line-of-the-c57bl-6j-mouse-strain-that-is-proficient-in-melatonin-synthesis
#12
Zhijing Zhang, Eduardo Silveyra, Nange Jin, Christophe P Ribelayga
The C57BL/6J (B6) is the most common inbred mouse strain used in biomedical research in the United States. Yet, this strain is notoriously known for being deficient in the biosynthesis of melatonin, an important effector of circadian clocks in the brain and in the retina. Melatonin deficiency in this strain results from non-functional alleles of the genes coding two key enzymes of the melatonin synthesis pathway: arylalkylamine-N-acetyltransferase (Aanat) and N-acetylserotonin-O-methyltransferase (Asmt). By introducing functional alleles of the Aanat and Asmt genes from the melatonin-proficient CBA/CaJ (CBA) mouse strain to B6, we have generated a B6 congenic line that has acquired the capacity of rhythmic melatonin synthesis...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29767307/virus-vector-mediated-genetic-modification-of-brain-tumor-stromal-cells-after-intravenous-delivery
#13
Adrienn Volak, Stanley G LeRoy, Jeya Shree Natasan, David J Park, Pike See Cheah, Andreas Maus, Zachary Fitzpatrick, Eloise Hudry, Kelsey Pinkham, Sheetal Gandhi, Bradley T Hyman, Dakai Mu, Dwijit GuhaSarkar, Anat O Stemmer-Rachamimov, Miguel Sena-Esteves, Christian E Badr, Casey A Maguire
The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively...
May 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29766225/potential-common-pathogenic-pathways-for-the-left-ventricular-noncompaction-cardiomyopathy-lvnc
#14
Ying Liu, Hanying Chen, Weinian Shou
Ventricular trabeculation and compaction are two essential morphogenetic events for generating a functionally competent ventricular wall. A significant reduction in trabeculation is usually associated with hypoplastic wall and ventricular compact zone deficiencies, which commonly leads to embryonic heart failure and early embryonic lethality. In contrast, the arrest of ventricular wall compaction (noncompaction) is believed to be causative to the left ventricular noncompaction (LVNC), a genetically heterogeneous disorder and the third most common cardiomyopathy among pediatric patients...
May 15, 2018: Pediatric Cardiology
https://www.readbyqxmd.com/read/29764837/il22-promotes-kras-mutant-lung-cancer-by-induction-of-a-pro-tumor-immune-response-and-protection-of-stemness-properties
#15
Nasim Khosravi, Mauricio S Caetano, Amber M Cumpian, Nese Unver, Cynthia De la Garza Ramos, Oscar Noble, Soudabeh Daliri, Belinda J Hernandez, Berenice A Gutierrez, Scott E Evans, Samir Hanash, Andrei M Alekseev, Yi Yang, Seon Hee Chang, Roza Nurieva, Humam Kadara, Jichao Chen, Edwin J Ostrin, Seyed Javad Moghaddam
Somatic KRAS mutations are the most common oncogenic variants in lung cancer and are associated with poor prognosis. Using a Kras-induced lung cancer mouse model, CC-LR, we previously showed a role for inflammation in lung tumorigenesis through activation of the NF-kB pathway, along with induction of interleukin 6 (IL6) and an IL17-producing CD4+ T-helper cell response. IL22 is an effector molecule secreted by CD4+ and γδ T cells that we previously found to be expressed in CC-LR mice. IL22 mostly signals through the STAT3 pathway and is thought to act exclusively on non-hematopoietic cells with basal IL22 receptor (IL22R) expression on epithelial cells...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29764806/temporal-efficacy-of-a-sulforaphane-based-broccoli-sprout-diet-in-prevention-of-breast-cancer-through-modulation-of-epigenetic-mechanisms
#16
Yuanyuan Li, Phillip Buckhaults, Shizhao Li, Trygve O Tollefsbol
Breast cancer is the most common cancer and the second leading cause of cancer death among women. An important risk factor for breast cancer is individual genetic background which is initially generated early in human life; for example, during the processes of embryogenesis and fetal development in utero. Bioactive dietary components such as sulforaphane (SFN), an isothiocyanate from cruciferous vegetables including broccoli sprouts (BSp), cabbage and kale, has been shown to reduce the risk of developing many common cancers through regulation of epigenetic mechanisms...
May 15, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29764566/laminopathies-mutations-on-single-gene-and-various-human-genetic-diseases
#17
So-Mi Kang, Min-Ho Yoon, Bum-Joon Park
Lamin A and its alternative splicing product Lamin C are the key intermediate filaments (IFs) of the inner nuclear membrane intermediate filament. Lamin A/C forms the inner nuclear mesh with Lamin B and works as a frame with a nuclear shape. In addition to supporting the function of nucleus, nuclear lamins perform important roles such as holding the nuclear pore complex and chromatin. However, mutations on the Lamin A or Lamin B related proteins induce various types of human genetic disorders and diseases including premature aging syndromes, muscular dystrophy, lipodystrophy and neuropathy...
May 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29764427/col4a5-and-lama5-variants-co-inherited-in-familial-hematuria-digenic-inheritance-or-genetic-modifier-effect
#18
Konstantinos Voskarides, Gregory Papagregoriou, Despina Hadjipanagi, Ioanelli Petrou, Isavella Savva, Avraam Elia, Yiannis Athanasiou, Androulla Pastelli, Maria Kkolou, Michalis Hadjigavriel, Christoforos Stavrou, Alkis Pierides, Constantinos Deltas
BACKGROUND: About 40-50% of patients with familial microscopic hematuria (FMH) caused by thin basement membrane nephropathy (TBMN) inherit heterozygous mutations in collagen IV genes (COL4A3, COL4A4). On long follow-up, the full phenotypic spectrum of these patients varies a lot, ranging from isolated MH or MH plus low-grade proteinuria to chronic renal failure of variable degree, including end-stage renal disease (ESRD). METHODS: Here, we performed Whole Exome Sequencing (WES) in patients of six families, presenting with autosomal dominant FMH, with or without progression to proteinuria and loss of renal function, all previously found negative for severe collagen IV mutations...
May 16, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29762513/spatiotemporal-labeling-of-melanocytes-in-mice
#19
REVIEW
Sarah Preston, Shweta Aras, M Raza Zaidi
Melanocytes are pigment producing cells in the skin that give rise to cutaneous malignant melanoma, which is a highly aggressive and the deadliest form of skin cancer. Studying melanocytes in vivo is often difficult due to their small proportion in the skin and the lack of specific cell surface markers. Several genetically-engineered mouse models (GEMMs) have been created to specifically label the melanocyte compartment. These models give both spatial and temporal control over the expression of a cellular 'beacon' that has an added benefit of inducible expression that can be activated on demand...
May 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29762036/biochemical-profiling-of-the-brain-and-blood-metabolome-in-a-mouse-model-of-prodromal-parkinson-s-disease-reveal-distinct-metabolic-profiles
#20
Stewart F Graham, Nowlen L Rey, Ali Yilmaz, Praveen Kumar, Zachary Madaj, Michael Maddens, Ray O Bahado-Singh, Katelyn Becker, Emily Schulz, Lindsay K Meyerdirk, Jennifer A Steiner, Jiyan Ma, Patrik Brundin
Parkinson's disease is the second most common neurodegenerative disease. In the vast majority of cases the origin is not genetic and the cause is not well understood, although progressive accumulation of α-synuclein aggregates appears central to the pathogenesis. Currently, treatments that slow disease progression are lacking and there are no robust biomarkers that can facilitate development of such treatments, or act as aids in early diagnosis. Therefore, we have defined metabolomic changes in the brain and serum in an animal model of prodromal Parkinson's disease...
May 15, 2018: Journal of Proteome Research
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