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Akita mice

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https://www.readbyqxmd.com/read/29777024/characterization-of-p-glycoprotein-humanized-mice-generated-by-chromosome-engineering-technology-its-utility-for-prediction-of-drug-distribution-to-the-brain-in-humans
#1
Yuki Yamasaki, Kaoru Kobayashi, Fuka Okuya, Naoyo Kajitani, Kanako Kazuki, Satoshi Abe, Shoko Takehara, Shingo Ito, Seiryo Ogata, Tatsuki Uemura, Sumio Ohtsuki, Genki Minegishi, Hidetaka Akita, Kan Chiba, Mitsuo Oshimura, Yasuhiro Kazuki
P-glycoprotein (P-gp), encoded by the MDR1 gene in humans and by the Mdr1a/1b genes in rodents, is expressed in numerous tissues and plays as an efflux pump to limit the distribution and absorption of many drugs. Owing to species differences of P-gp between humans and rodents, it is difficult to predict the impact of P-gp on pharmacokinetics and tissue distribution of P-gp substrates in humans from results of animal experiments. Therefore, we generated a novel P-gp humanized mouse model by using a mouse artificial chromosome (MAC) vector [designated human MDR1-MAC (hMDR1-MAC) mice]...
May 18, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29761600/loss-of-angiotensin-converting-enzyme-2-exacerbates-diabetic-retinopathy-by-promoting-bone-marrow-dysfunction
#2
Yaqian Duan, Eleni Beli, Sergio Li Calzi, Judith L Quigley, Rehae C Miller, Leni Moldovan, Dongni Feng, Tatiana E Salazar, Sugata Hazra, Jude Al-Sabah, Kakarla V Chalam, Thao Le Phuong Trinh, Marya Meroueh, Troy A Markel, Matthew C Murray, Ruchi J Vyas, Michael E Boulton, Patricia Parsons-Wingerter, Gavin Y Oudit, Alexander G Obukhov, Maria B Grant
Angiotensin-converting enzyme 2 (ACE2) is the primary enzyme of the vasoprotective axis of the renin angiotensin system (RAS). We tested the hypothesis that loss of ACE2 would exacerbate diabetic retinopathy by promoting bone marrow dysfunction. ACE2-/y were crossed with Akita mice, a model of type 1 diabetes. When comparing the bone marrow of the ACE2-/y -Akita mice to that of Akita mice, we observed a reduction of both short-term and long-term repopulating hematopoietic stem cells, a shift of hematopoiesis towards myelopoiesis, and an impairment of lineage- c-kit+ hematopoietic stem/progenitor cell (HS/PC) migration and proliferation...
May 15, 2018: Stem Cells
https://www.readbyqxmd.com/read/29675273/assessment-of-global-and-local-alterations-in-retinal-layer-thickness-in-ins2-akita-diabetic-mice-by-spectral-domain-optical-coherence-tomography
#3
Andrew W Francis, Justin Wanek, Mahnaz Shahidi
Purpose/Aim: The Ins2 (Akita) mouse is a spontaneous diabetic mouse model with a heterozygous mutation in the insulin 2 gene that results in sustained hyperglycemia. The purpose of the study was to assess global and local retinal layer thickness alterations in Akita mice by analysis of spectral domain optical coherence tomography (SD-OCT) images. Materials and Methods: SD-OCT imaging was performed in Akita and wild-type mice at 12 and 24 weeks of age. Inner retinal thickness (IRT), outer retinal thickness (ORT), total retinal thickness (TRT), and photoreceptor outer segment length (OSL) were measured...
2018: Journal of Ophthalmology
https://www.readbyqxmd.com/read/29674975/possible-role-of-nadph-oxidase-4-in-angiotensin-ii-induced-muscle-wasting-in-mice
#4
Tomoyasu Kadoguchi, Kazunori Shimada, Hiroshi Koide, Tetsuro Miyazaki, Tomoyuki Shiozawa, Shuhei Takahashi, Tatsuro Aikawa, Shohei Ouchi, Kenichi Kitamura, Yurina Sugita, Al Shahi Hamad, Mitsuhiro Kunimoto, Yayoi Sato-Okabayashi, Koji Akita, Kikuo Isoda, Hiroyuki Daida
Background: Muscle wasting is a debilitating phenotype associated with chronic heart failure (CHF). We have previously demonstrated that angiotensin II (AII) directly induces muscle wasting in mice through the activation of NADPH oxidase (Nox). In this study, we tested the hypothesis that deficiency of NADPH oxidase 4 (Nox4), a major source of oxidative stress, ameliorates AII-induced muscle wasting through the regulation of redox balance. Methods and Results: Nox4 knockout (KO) and wild-type (WT) mice were used...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29519924/aminopeptidase-n-cd13-as-a-potential-therapeutic-target-in-malignant-pleural-mesothelioma
#5
Takahiko Otsuki, Taku Nakashima, Hironobu Hamada, Yusuke Takayama, Shin Akita, Takeshi Masuda, Yasushi Horimasu, Shintaro Miyamoto, Hiroshi Iwamoto, Kazunori Fujitaka, Yoshihiro Miyata, Masayuki Miyake, Nobuoki Kohno, Morihito Okada, Noboru Hattori
Angiogenesis is a crucial factor in the progression of malignant pleural mesothelioma (MPM), and antiangiogenic strategies might be effective against MPM. Aminopeptidase N/CD13 (APN/CD13) promotes tumour angiogenesis and is associated with poor prognosis; however, its clinical significance in MPM remains unclear.In 37 consecutive patients with surgically resected MPM, we evaluated the association between immunohistochemical APN/CD13 expression in resected tumours and survival. Additionally, the antitumour and antiangiogenic effects of MT95-4, a fully humanized anti-APN/CD13 monoclonal antibody, were evaluated in mice orthotopically implanted with EHMES-10 (abundantly expressing APN/CD13) and MSTO-211H (scarcely expressing APN/CD13) MPM cells...
March 8, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29491222/cancer-type-oatp1b3-mrna-in-extracellular-vesicles-as-a-promising-candidate-for-a-serum-based-colorectal-cancer-biomarker
#6
Hanae Morio, Yuchen Sun, Manami Harada, Hideyuki Ide, Osamu Shimozato, Xujia Zhou, Kenjirou Higashi, Ryuzaburo Yuki, Naoto Yamaguchi, Josefina Piñón Hofbauer, Christina Guttmann-Gruber, Naohiko Anzai, Hidetaka Akita, Kan Chiba, Tomomi Furihata
Cancer-type organic anion transporting polypeptide 1B3 (Ct-OATP1B3) mRNA is a variant isoform of the liver-type OATP1B3. Because Ct-OATP1B3 mRNA shows an excellent cancer-specific expression profile in colorectal cancer (CRC), and that its expression levels are associated with CRC prognosis, it holds the potential to become a useful CRC detection and diagnosis biomarker. While the potential is currently justified only at the tissue level, if existence of Ct-OATP1B3 mRNA in CRC-derived extracellular vesicles (EVs) is validated, the findings could enhance its translational potential as a CRC detection and diagnosis biomarker...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29482192/type-i-diabetic-akita-mouse-model-is-characterized-by-abnormal-cardiac-deformation-during-early-stages-of-diabetic-cardiomyopathy-with-speckle-tracking-based-strain-imaging
#7
Yingchao Zhou, Hong Xiao, Jianfei Wu, Lingfeng Zha, Mengchen Zhou, Qianqian Li, Mengru Wang, Shumei Shi, Yanze Li, Liangkun Lyu, Qing Wang, Xin Tu, Qiulun Lu
BACKGROUND/AIMS: Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages. METHODS: Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29434227/the-nlrp3-inflammasome-may-contribute-to-pathologic-neovascularization-in-the-advanced-stages-of-diabetic-retinopathy
#8
Shyam S Chaurasia, Rayne R Lim, Bhav H Parikh, Yeo Sia Wey, Bo Bo Tun, Tien Yin Wong, Chi D Luu, Rupesh Agrawal, Arkasubhra Ghosh, Alessandra Mortellaro, Elizabeth Rackoczy, Rajiv R Mohan, Veluchamy A Barathi
Diabetic retinopathy (DR) is a retinal microvascular disease characterized by inflammatory and angiogenic pathways. In this study, we evaluated NLRP3 inflammasome in a double transgenic mouse model, Akimba (Ins2 Akita xVEGF+/- ), which demonstrates hyperglycemia, vascular hyperpermeability and neovascularization seen in the proliferative DR. Retinal structural integrity, vascular leakage and function were examined by fundus photography, fluorescein angiography, optical coherence tomography, retinal flat mounts, laser speckle flowgraphy (LSFG), and electroretinography in Akimba and its parental strains, Akita (Ins2 Akita ) and Kimba (trVEGF029) mice...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29404442/generation-of-safe-and-therapeutically-effective-human-induced-pluripotent-stem-cell-derived-hepatocyte-like-cells-for-regenerative-medicine
#9
Kazuo Takayama, Naoki Akita, Natsumi Mimura, Rina Akahira, Yukimasa Taniguchi, Makoto Ikeda, Fuminori Sakurai, Osamu Ohara, Tomohiro Morio, Kiyotoshi Sekiguchi, Hiroyuki Mizuguchi
Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells are expected to be applied for regenerative medicine. In this study, we attempted to generate safe and therapeutically effective human iPS-HLCs for hepatocyte transplantation. First, human iPS-HLCs were generated from a human leukocyte antigen-homozygous donor on the assumption that the allogenic transplantation might be carried out. Highly efficient hepatocyte differentiation was performed under a feeder-free condition using human recombinant laminin 111, laminin 511, and type IV collagen...
December 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29394991/biallelic-variants-in-cnpy3-encoding-an-endoplasmic-reticulum-chaperone-cause-early-onset-epileptic-encephalopathy
#10
Hiroki Mutoh, Mitsuhiro Kato, Tenpei Akita, Takuma Shibata, Hiroyuki Wakamoto, Hiroko Ikeda, Hiroki Kitaura, Kazushi Aoto, Mitsuko Nakashima, Tianying Wang, Chihiro Ohba, Satoko Miyatake, Noriko Miyake, Akiyoshi Kakita, Kensuke Miyake, Atsuo Fukuda, Naomichi Matsumoto, Hirotomo Saitsu
Early-onset epileptic encephalopathies, including West syndrome (WS), are a group of neurological disorders characterized by developmental impairments and intractable seizures from early infancy. We have now identified biallelic CNPY3 variants in three individuals with WS; these include compound-heterozygous missense and frameshift variants in a family with two affected siblings (individuals 1 and 2) and a homozygous splicing variant in a consanguineous family (individual 3). All three individuals showed hippocampal malrotation...
January 26, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29348593/temporal-diabetes-induced-biochemical-changes-in-distinctive-layers-of-mouse-retina
#11
Ebrahim Aboualizadeh, Christine M Sorenson, Alex J Schofield, Miriam Unger, Nader Sheibani, Carol J Hirschmugl
To discover the mechanisms underlying the progression of diabetic retinopathy (DR), a more comprehensive understanding of the biomolecular processes in individual retinal cells subjected to hyperglycemia is required. Despite extensive studies, the changes in the biochemistry of retinal layers during the development of DR are not well known. In this study, we aimed to determine a more detailed understanding of the natural history of DR in Akita/+ (type 1 diabetes model) male mice with different duration of diabetes...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29304075/%C3%AE-cell-specific-overexpression-of-adiponectin-receptor-1-does-not-improve-diabetes-mellitus-in-akita-mice
#12
Jungmi Choi, Hatasu Kobayashi, Hiroko Okuda, Kouji H Harada, Midori Takeda, Hiroyuki Fujimoto, Shunsuke Yamane, Daisuke Tanaka, Shohab Youssefian, Nobuya Inagaki, Akio Koizumi
Adiponectin, a metabolically-active cytokine secreted from adipose tissue, is reported to have anti-apoptotic effects on β-cells as well as anti-hyperglycemic effects through adiponectin receptor signaling. However, the anti-apoptotic effects of adiponectin on β-cells have not been confirmed in established diabetic models, and the anti-hyperglycemic effects and their associated signal cascades remain controversial. To investigate the effects of adiponectin on β-cell protection and its down-stream signaling events, we have generated β-cell-specific rat insulin promoter (RIP)-AdipoR1 transgenic mice (AdipoR1 mice), in which the adiponectin receptor, AdipoR1, is overexpressed in β-cells in a manner synchronous with insulin demand...
2018: PloS One
https://www.readbyqxmd.com/read/29211853/nrf2-deficiency-upregulates-intrarenal-angiotensin-converting-enzyme-2-and-angiotensin-1-7-receptor-expression-and-attenuates-hypertension-and-nephropathy-in-diabetic-mice
#13
Shuiling Zhao, Anindya Ghosh, Chao-Sheng Lo, Isabelle Chenier, James W Scholey, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
We investigated the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in renin-angiotensin system (RAS) gene expression in renal proximal tubule cells (RPTCs) and in the development of systemic hypertension and kidney injury in diabetic Akita mice. We used adult male Akita Nrf2 knockout mice and Akita mice treated with trigonelline (an Nrf2 inhibitor) or oltipraz (an Nrf2 activator). We also examined rat immortalized RPTCs (IRPTCs) stably transfected with control plasmids or plasmids containing rat angiotensinogen (Agt), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (Ace2), or angiotensin 1-7 (Ang 1-7) receptor (MasR) gene promoters...
February 1, 2018: Endocrinology
https://www.readbyqxmd.com/read/29203863/orai-channels-are-critical-for-receptor-mediated-endocytosis-of-albumin
#14
Bo Zeng, Gui-Lan Chen, Eliana Garcia-Vaz, Sunil Bhandari, Nikoleta Daskoulidou, Lisa M Berglund, Hongni Jiang, Thomas Hallett, Lu-Ping Zhou, Li Huang, Zi-Hao Xu, Viji Nair, Robert G Nelson, Wenjun Ju, Matthias Kretzler, Stephen L Atkin, Maria F Gomez, Shang-Zhong Xu
Impaired albumin reabsorption by proximal tubular epithelial cells (PTECs) has been highlighted in diabetic nephropathy (DN), but little is known about the underlying molecular mechanisms. Here we find that ORAI1-3, are preferentially expressed in PTECs and downregulated in patients with DN. Hyperglycemia or blockade of insulin signaling reduces the expression of ORAI1-3. Inhibition of ORAI channels by BTP2 and diethylstilbestrol or silencing of ORAI expression impairs albumin uptake. Transgenic mice expressing a dominant-negative Orai1 mutant (E108Q) increases albuminuria, and in vivo injection of BTP2 exacerbates albuminuria in streptozotocin-induced and Akita diabetic mice...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29203613/-nfe2l1-silenced-insulinoma-cells-acquire-aggressiveness-and-chemoresistance
#15
Jingqi Fu, Hongzhi Zheng, Qi Cui, Chengjie Chen, Simeng Bao, Jing Sun, Lu Li, Bei Yang, Huihui Wang, Yongyong Hou, Yuanyuan Xu, Yuanhong Xu, Qiang Zhang, Jingbo Pi
The transcription factor nuclear factor erythroid 2-like 1 (NFE2L1 or NRF1) is involved in various critical cell processes such as maintenance of ubiquitin-proteasome system and regulation of the cellular antioxidant response. We previously determined that pancreatic β-cell-specific Nfe2l1 -knockout mice had hyperinsulinemia and that silencing of Nfe2l1 in mouse islets or MIN6 insulinoma β-cells induced elevated basal insulin release and altered glucose metabolism. Hypoglycemia is a major issue with aggressive insulinomas, although a role of NFE2L1 in this pathology is not defined...
March 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29186067/immunohistochemical-characterization-of-connexin43-expression-in-a-mouse-model-of-diabetic-retinopathy-and-in-human-donor-retinas
#16
Odunayo O Mugisho, Colin R Green, Jie Zhang, Nicolette Binz, Monica L Acosta, Elizabeth Rakoczy, Ilva D Rupenthal
Diabetic retinopathy (DR) develops due to hyperglycemia and inflammation-induced vascular disruptions in the retina with connexin43 expression patterns in the disease still debated. Here, the effects of hyperglycemia and inflammation on connexin43 expression in vitro in a mouse model of DR and in human donor tissues were evaluated. Primary human retinal microvascular endothelial cells (hRMECs) were exposed to high glucose (HG; 25 mM) or pro-inflammatory cytokines IL-1β and TNF-α (10 ng/mL each) or both before assessing connexin43 expression...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29061652/progressive-renal-disease-established-by-renin-coding-adeno-associated-virus-driven-hypertension-in-diverse-diabetic-models
#17
Shannon M Harlan, Kathleen M Heinz-Taheny, John M Sullivan, Tao Wei, Hana E Baker, Dianna L Jaqua, Zhonghua Qi, Martin S Cramer, Tatiyana L Shiyanova, Matthew D Breyer, Josef G Heuer
Progress in research and developing therapeutics to prevent diabetic kidney disease (DKD) is limited by a lack of animal models exhibiting progressive kidney disease. Chronic hypertension, a driving factor of disease progression in human patients, is lacking in most available models of diabetes. We hypothesized that superimposition of hypertension on diabetic mouse models would accelerate DKD. To test this possibility, we induced persistent hypertension in three mouse models of type 1 diabetes and two models of type 2 diabetes by adeno-associated virus delivery of renin (ReninAAV)...
February 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29043461/effect-of-anti-angiogenesis-induced-by-chemotherapeutic-monotherapy-chemotherapeutic-bisphosphonate-combination-therapy-and-anti-vegfa-mab-therapy-on-tooth-extraction-socket-healing-in-mice
#18
Yuri Akita, Shinichiro Kuroshima, Kazunori Nakajima, Hiroki Hayano, Riho Kanai, Muneteru Sasaki, Takashi Sawase
Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly occurs in oncology patients receiving chemotherapeutic agents and bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates on wound healing after tooth extraction remains unknown. The aim of this study was to determine the precise etiology of ONJ induced by chemotherapy and bisphosphonate combination therapy. Mice received zoledronate (ZA) monotherapy, cyclophosphamide (CY) monotherapy or CY/ZA combination therapy...
October 17, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28883608/gyy4137-a-hydrogen-sulfide-donor-modulates-mir194-dependent-collagen-realignment-in-diabetic-kidney
#19
A M Sashi Papu John, Sourav Kundu, Sathnur Pushpakumar, Maura Fordham, Gregory Weber, Manas Mukhopadhyay, Utpal Sen
The relationship between hydrogen sulfide (H2S), microRNAs (miRs), matrix metalloproteinases (MMPs) and poly-ADP-ribose-polymerase-1 (PARP-1) in diabetic kidney remodeling remains mostly obscured. We aimed at investigating whether alteration of miR-194-dependent MMPs and PARP-1 causes renal fibrosis in diabetes kidney, and whether H2S ameliorates fibrosis. Wild type, diabetic Akita mice as well as mouse glomerular endothelial cells (MGECs) were used as experimental models, and GYY4137 as H2S donor. In diabetic mice, plasma H2S levels were decreased while ROS and expression of its modulator (ROMO1) were increased...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28837672/cardiac-transcriptome-profiling-of-diabetic-akita-mice-using-microarray-and-next-generation-sequencing
#20
Varun Kesherwani, Hamid R Shahshahan, Paras K Mishra
Although diabetes mellitus (DM) causes cardiomyopathy and exacerbates heart failure, the underlying molecular mechanisms for diabetic cardiomyopathy/heart failure are poorly understood. Insulin2 mutant (Ins2+/-) Akita is a mouse model of T1DM, which manifests cardiac dysfunction. However, molecular changes at cardiac transcriptome level that lead to cardiomyopathy remain unclear. To understand the molecular changes in the heart of diabetic Akita mice, we profiled cardiac transcriptome of Ins2+/- Akita and Ins2+/+ control mice using next generation sequencing (NGS) and microarray, and determined the implications of differentially expressed genes on various heart failure signaling pathways using Ingenuity pathway (IPA) analysis...
2017: PloS One
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