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https://www.readbyqxmd.com/read/28929374/inhibition-of-gsk-3%C3%AE-activation-protects-sd-rat-retina-against-n-methyl-n-nitrosourea-induced-degeneration-by-modulating-the-wnt-%C3%AE-catenin-signaling-pathway
#1
Baoying Wang, Chenghu Hu, Xiaobei Yang, Fangying Du, Yan Feng, Hongbo Li, Chunhui Zhu, Xiaorui Yu
Retinal degenerative diseases are characterized by photoreceptor cell loss. Photoreceptor cell loss leading to retinal degeneration can be induced by N-methyl-N-nitrosourea (MNU), which was widely used to mimic the pathology. However, the mechanism by which MNU induces photoreceptor cell loss is still largely unknown. The purpose of the present study was to investigate whether phosphorylation of glycogen synthase kinase-3β (p-GSK-3β) is a potent mediator of MNU-induced retinal degeneration and how p-GSK-3β affects the process...
September 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28921690/tissue-specific-and-time-dependent-clonal-expansion-of-enu-induced-mutant-cells-in-gpt-delta-mice
#2
Takafumi Nakayama, Tomoko Sawai, Ikuko Masuda, Shinya Kaneko, Kazumi Yamauchi, Benjamin J Blyth, Yoshiya Shimada, Akira Tachibana, Shizuko Kakinuma
DNA mutations play a crucial role in the origins of cancer, and the clonal expansion of mutant cells is one of the fundamental steps in multistage carcinogenesis. In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N-ethyl-N-nitrosourea (ENU) with the persistence of ENU-induced mutant clones in transgenic gpt delta B6C3F1 mice. The induced gpt mutations afforded no selective advantage in the mouse cells and could be distinguished by a mutational spectrum that is characteristic of ENU treatment...
September 16, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28917524/tremor-dominant-kyoto-trdk-rats-carry-a-missense-mutation-in-the-gene-encoding-the-sk2-subunit-of-small-conductance-ca-2-activated-k-channel
#3
Takashi Kuramoto, Mayuko Yokoe, Naofumi Kunisawa, Kana Ohashi, Takahito Miyake, Yuki Higuchi, Kazuto Yoshimi, Tomoji Mashimo, Miyuu Tanaka, Mitusru Kuwamura, Shuji Kaneko, Saki Shimizu, Tadao Serikawa, Yukihiro Ohno
Tremor dominant Kyoto (Trdk) is an autosomal dominant mutation that appeared in F344/NSlc rats mutagenized with N-ethyl-N-nitrosourea (ENU). In this study, we characterized and genetically analyzed F344-Trdk/+ heterozygous rats. The rats exhibited a tremor that was especially evident around weaning but persisted throughout life. The tremors of F344-Trdk/+ rats were attenuated by drugs effective against essential tremor (ET) but not drugs used to treat Parkinson's disease-related tremor, indicating that the pharmacological phenotype of F344-Trdk/+ rats was similar to human ET...
September 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28916862/monitoring-the-response-of-urothelial-precancerous-lesions-to-bacillus-calmette-guerin-at-the-proteome-level-in-an-in-vivo-rat-model
#4
Kerem Teke, Nil Guzel, Ali Kemal Uslubas, Murat Kasap, Hasan Yilmaz, Gurler Akpinar, Demir Kursat Yildiz, Ozdal Dillioglugil
Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. We aimed to monitor changes at the proteome level to identify putative protein biomarkers associated with the response of urothelial precancerous lesions to intravesical BCG treatment. The rats were divided into three groups (n = 10/group): control, non-treated, and BCG-treated groups. The non-treated and BCG-treated groups received N-methyl-N-nitrosourea intravesically. BCG Tice-strain was instilled into bladder in BCG-treated group...
September 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28916811/an-enu-induced-splice-site-mutation-of-mouse-col1a1-causing-recessive-osteogenesis-imperfecta-and-revealing-a-novel-splicing-rescue
#5
Koichi Tabeta, Xin Du, Kei Arimatsu, Mai Yokoji, Naoki Takahashi, Norio Amizuka, Tomoka Hasegawa, Karine Crozat, Tomoki Maekawa, Sayuri Miyauchi, Yumi Matsuda, Takako Ida, Masaru Kaku, Kasper Hoebe, Kinji Ohno, Hiromasa Yoshie, Kazuhisa Yamazaki, Eva Marie Y Moresco, Bruce Beutler
GU-AG consensus sequences are used for intron recognition in the majority of cases of pre-mRNA splicing in eukaryotes. Mutations at splice junctions often cause exon skipping, short deletions, or insertions in the mature mRNA, underlying one common molecular mechanism of genetic diseases. Using N-ethyl-N-nitrosourea, a novel recessive mutation named seal was produced, associated with fragile bones and susceptibility to fractures (spine and limbs). A single nucleotide transversion (T → A) at the second position of intron 36 of the Col1a1 gene, encoding the type I collagen, α1 chain, was responsible for the phenotype...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900397/the-comparative-efficiency-of-intraperitoneal-and-intravitreous-injection-of-hydrogen-rich-saline-against-n-methyl-n-nitrosourea-induced-retinal-degeneration-a-topographic-study
#6
Ye Tao, Tao Chen, Wei Fang, Zhongjun Yan, Qinghua Yang, Yifei Huang, Linjun Yu, Lingling Fan
Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited retinal diseases leading to blindness. The present study explored the protective effects of hydrogen rich saline (HRS) against the photoreceptor degeneration in the N-Methyl-N-nitrosourea (MNU) administrated rat, a pharmacologically induced RP model. The therapeutic effects of intraperitoneal (IP) and intravitreous (IV) injections of HRS on regional retina was quantified via topographic measurements. The MNU administrated rats received IV or IP injections of HRS, and then they were subjected to electroretinography, multi electrode array, histological and immunohistochemistry examinations...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28894906/whole-exome-sequencing-reveals-a-functional-mutation-in-the-gain-domain-of-the-bai2-receptor-underlying-a-forward-mutagenesis-hyperactivity-qtl
#7
David J Speca, James S Trimmer, Andrew S Peterson, Elva Díaz
The identification of novel genes underlying complex mouse behavioral traits remains an important step in understanding normal brain function and its dysfunction in mental health disorders. To identify dominant mutations that influence locomotor activity, we performed a mouse N-ethyl-N-nitrosourea (ENU) forward mutagenesis screen and mapped several loci as quantitative traits. Here we describe the fine-mapping and positional cloning of a hyperactivity locus mapped to the medial portion of mouse chromosome four...
September 12, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28891332/subretinal-delivery-of-erythropoietin-alleviates-the-n-methyl-n-nitrosourea-induced-photoreceptor-degeneration-and-visual-functional-impairments-an-in-vivo-and-ex-vivo-study
#8
Ye Tao, Yue Wang, Zhao Ma, Liqiang Wang, Limin Qin, Lu Wang, Yi Fei Huang, Shizhong Zhang
Retinitis pigmentosa (RP) is a heterogeneous group hereditary retinal disease that is characterized by photoreceptor degeneration. The present study sought to explore the therapeutic effects of erythropoietin (EPO) on the N-methyl-N-nitrosourea (MNU)-induced photoreceptor degeneration. The MNU-administered mouse or normal control received a subretinal injection of EPO (at the dose of 10U). Twenty-four hours after EPO injection, the retinal EPO levels of experimental animals were quantified. Subsequently, the experimental animals were subjected to optokinetic tests, ERG examination, SD-OCT examination, histology assessment, and immunohistochemistry evaluation...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28853066/phenotypical-characteristics-of-chemically-induced-mammary-tumor
#9
A V Kabakov, A P Lykov, D V Morozov, O V Kazakov, A F Poveshchenko, T V Raiter, D N Strunkin, V I Konenkov
The histological and immunohistochemical type of chemically induced (injection of N-methyl-N-nitrosourea into the mammary gland) breast tumor was studied in Wistar females. The tumor induced by N-methyl-N-nitrosourea was moderately differentiated adenocarcinoma with infiltrative growth lacking estrogen-α and human epidermal growth factor receptors, and expressing progesterone receptors; tumor cells were characterized by high proliferative activity. This variant of chemically induced breast tumor corresponds to human breast cancer luminal type B...
August 29, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28827327/sensitized-mutagenesis-screen-in-factor-v-leiden-mice-identifies-thrombosis-suppressor-loci
#10
Randal J Westrick, Kärt Tomberg, Amy E Siebert, Guojing Zhu, Mary E Winn, Sarah L Dobies, Sara L Manning, Marisa A Brake, Audrey C Cleuren, Linzi M Hobbs, Lena M Mishack, Alexander J Johnston, Emilee Kotnik, David R Siemieniak, Jishu Xu, Jun Z Li, Thomas L Saunders, David Ginsburg
Factor V Leiden (F5(L) ) is a common genetic risk factor for venous thromboembolism in humans. We conducted a sensitized N-ethyl-N-nitrosourea (ENU) mutagenesis screen for dominant thrombosuppressor genes based on perinatal lethal thrombosis in mice homozygous for F5(L) (F5(L/L) ) and haploinsufficient for tissue factor pathway inhibitor (Tfpi(+/-) ). F8 deficiency enhanced the survival of F5(L/L)Tfpi(+/-) mice, demonstrating that F5(L/L)Tfpi(+/-) lethality is genetically suppressible. ENU-mutagenized F5(L/L) males and F5(L/+)Tfpi(+/-) females were crossed to generate 6,729 progeny, with 98 F5(L/L)Tfpi(+/-) offspring surviving until weaning...
August 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28820464/enhanced-susceptibility-of-ogg1-mutant-mice-to-multiorgan-carcinogenesis
#11
Anna Kakehashi, Naomi Ishii, Takahiro Okuno, Masaki Fujioka, Min Gi, Hideki Wanibuchi
The role of deficiency of oxoguanine glycosylase 1 (Ogg1) Mmh homolog, a repair enzyme of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) residue in DNA, was investigated using the multiorgan carcinogenesis bioassay in mice. A total of 80 male and female six-week-old mice of C57BL/6J background carrying a mutant Mmh allele of the Mmh/Ogg1 gene (Ogg1(-)(/)(-)) and wild type (Ogg1(+/+)) mice were administered N-diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), N-bis (2-hydroxypropyl) nitrosamine (DHPN) and 1,2-dimethylhydrazine dihydrochloride (DMH) (DMBDD) to induce carcinogenesis in multiple organs, and observed up to 34 weeks...
August 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28807016/endogenous-controls-of-gene-expression-in-n-methyl-n-nitrosourea-induced-t-cell-lymphoma-in-p53-deficient-mice
#12
Xi Wu, Susu Liu, Jianjun Lyu, Shuya Zhou, Yanwei Yang, Chenfei Wang, Wenda Gu, Qin Zuo, Baowen Li, Changfa Fan
BACKGROUND: Real-time polymerase chain reaction (PCR) has become an increasingly important technique for gene expression profiling because it can provide insights into complex biological and pathological processes and be used to predict disease or treatment outcomes. Although normalized data are necessary for an accurate estimation of mRNA expression levels, several pieces of evidence suggest that the expression of so-called housekeeping genes is not stable. This study aimed to validate reference genes for the normalization of real-time PCR in an N-methyl-N-nitrosourea (MNU)-induced T-cell lymphoma mouse model...
August 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28806779/a-mutation-in-nischarin-causes-otitis-media-via-limk1-and-nf-%C3%AE%C2%BAb-pathways
#13
Michael Crompton, Tom Purnell, Hayley E Tyrer, Andrew Parker, Greg Ball, Rachel E Hardisty-Hughes, Richard Gale, Debbie Williams, Charlotte H Dean, Michelle M Simon, Ann-Marie Mallon, Sara Wells, Mahmood F Bhutta, Martin J Burton, Hilda Tateossian, Steve D M Brown
Otitis media (OM), inflammation of the middle ear (ME), is a common cause of conductive hearing impairment. Despite the importance of the disease, the aetiology of chronic and recurrent forms of middle ear inflammatory disease remains poorly understood. Studies of the human population suggest that there is a significant genetic component predisposing to the development of chronic OM, although the underlying genes are largely unknown. Using N-ethyl-N-nitrosourea mutagenesis we identified a recessive mouse mutant, edison, that spontaneously develops a conductive hearing loss due to chronic OM...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28797121/non-alcoholic-fatty-liver-disease-in-mice-with-heterozygous-mutation-in-tmed2
#14
Wenyang Hou, Swati Gupta, Marie-Claude Beauchamp, Libin Yuan, Loydie A Jerome-Majewska
The transmembrane emp24 domain/p24 (TMED) family are essential components of the vesicular transport machinery. Members of the TMED family serve as cargo receptors implicated in selection and packaging of endoplasmic reticulum (ER) luminal proteins into coatomer (COP) II coated vesicles for anterograde transport to the Golgi. Deletion or mutations of Tmed genes in yeast and Drosophila results in ER-stress and activation of the unfolded protein response (UPR). The UPR leads to expression of genes and proteins important for expanding the folding capacity of the ER, degrading misfolded proteins, and reducing the load of new proteins entering the ER...
2017: PloS One
https://www.readbyqxmd.com/read/28751539/mechanisms-of-resistance-to-ntrk-inhibitors-and-therapeutic-strategies-in-ntrk1-rearranged-cancers
#15
Miho J Fuse, Koutaroh Okada, Tomoko Oh-Hara, Hayato Ogura, Naoya Fujita, Ryohei Katayama
Neurotrophic receptor tyrosine kinase 1 (NTRK1) gene rearrangement leads to constitutive activation of NTRK1, which induces high transforming ability. NTRK-rearranged cancers have been identified in several cancer types, such as glioblastoma, non-small-cell lung cancer, and colorectal cancer. Although there are currently no clinically approved inhibitors that target NTRK1, several tyrosine kinase inhibitors (TKIs), such as entrectinib and LOXO-101, are in clinical trials. The purpose of this study was to identify potential mechanisms of resistance to NTRK inhibitors and find potential therapeutic strategies to overcome the resistance...
July 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28744879/procarbazine-lomustine-and-vincristine-for-recurrent-high-grade-glioma
#16
REVIEW
Saurabh Parasramka, Goutham Talari, Myrna Rosenfeld, Jing Guo, John L Villano
BACKGROUND: Recurrent high-grade glioma (HGG) carries an extremely poor prognosis. There is no current standard of care or guideline-based recommendations. Nitrosourea-based multidrug chemotherapy or PCV - procarbazine, lomustine (CCNU) and vincristine - is one of the treatment options at recurrence. There has been no meta-analysis which looks at the benefits and harms of PCV chemotherapy in adults with recurrent HGG. OBJECTIVES: To assess the effectiveness and safety of procarbazine, lomustine, and vincristine (PCV) chemotherapy with other interventions in adults with recurrent high-grade glioma...
July 26, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28717217/tki-addicted-ros1-rearranged-cells-are-destined-to-survival-or-death-by-the-intensity-of-ros1-kinase-activity
#17
Hayato Ogura, Yuka Nagatake-Kobayashi, Jun Adachi, Takeshi Tomonaga, Naoya Fujita, Ryohei Katayama
ROS1 rearrangement is observed in 1-2% of non-small cell lung cancers (NSCLC). The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has induced marked tumour shrinkage in ROS1-rearranged cancers. However, emergence of acquired resistance to TKI is inevitable within a few years. Previous findings indicate that cabozantinib overcomes secondary mutation-mediated crizotinib-resistance in ROS1-fusion-positive cells. Here we attempted to establish cabozantinib-resistant cells by N-ethyl-N-nitrosourea mutagenesis screening using CD74-ROS1-expressing Ba/F3 cells...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714084/applying-the-erythrocyte-pig-a-assay-concept-to-rat-epididymal-sperm-for-germ-cell-mutagenicity-evaluation
#18
Zhiying Ji, Matthew J LeBaron
The Pig-a assay, a recently developed in vivo somatic gene mutation assay, is based on the identification of mutant erythrocytes that have an altered repertoire of glycosylphosphatidylinositol (GPI)-anchored cell surface markers. We hypothesized that the erythrocyte Pig-a assay concept could be applied to rat cauda epididymal spermatozoa (sperm) for germ cell mutagenicity evaluation. We used GPI-anchored CD59 as the Pig-a mutation marker and examined the frequency of CD59-negative sperm using flow cytometry...
August 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28711606/ovarian-aromatase-loss-of-function-mutant-medaka-undergo-ovary-degeneration-and-partial-female-to-male-sex-reversal-after-puberty
#19
Masatoshi Nakamoto, Yasushi Shibata, Kaoru Ohno, Takeshi Usami, Yasuhiro Kamei, Yoshihito Taniguchi, Takeshi Todo, Takashi Sakamoto, Graham Young, Penny Swanson, Kiyoshi Naruse, Yoshitaka Nagahama
Although estrogens have been generally considered to play a critical role in ovarian differentiation in non-mammalian vertebrates, the specific functions of estrogens during ovarian differentiation remain unclear. We isolated two mutants with premature stops in the ovarian aromatase (cyp19a1) gene from an N-ethyl-N-nitrosourea-based gene-driven mutagenesis library of the medaka, Oryzias latipes. In XX mutants, gonads first differentiated into normal ovaries containing many ovarian follicles that failed to accumulate yolk...
July 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28694663/inhibition-of-n-methyl-n-nitrosourea-induced-gastric-tumorigenesis-by-liuwei-dihuang-pill-in-db-db-mice
#20
Shan Zhuang, Yong-Mei Jian, Yong-Ning Sun
AIM: To investigate the inhibitory effect of Liuwei Dihuang Pill (LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea (MNU) in diabetic mice. METHODS: Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP...
June 21, 2017: World Journal of Gastroenterology: WJG
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