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Disease Models & Mechanisms

Maria Angeles Marques-Torrejon, Ester Gangoso, Steven M Pollard
Glioblastoma (GBM) is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as GBM stem cells (GSCs). Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human)...
December 1, 2017: Disease Models & Mechanisms
Sree Deepthi Muthukrishnan, Sergey Ryzhov, Michele Karolak, Leif Oxburgh
The final nephron number in an adult kidney is regulated by nephron progenitor cell availability and collecting duct branching in the fetal period. Fetal environmental perturbations that cause reductions in cell numbers in these two compartments result in low nephron endowment. Previous work has shown that maternal dietary factors influence nephron progenitor cell availability, with both caloric restriction and protein deprivation leading to reduced cell numbers through apoptosis. In this study, we evaluate the consequences of inducing nephron progenitor cell death on progenitor niche dynamics and on nephron endowment...
December 1, 2017: Disease Models & Mechanisms
Hanna Luukinen, Milka Marjut Hammarén, Leena-Maija Vanha-Aho, Aleksandra Svorjova, Laura Kantanen, Sampsa Järvinen, Bruno Vincent Luukinen, Eric Dufour, Mika Rämet, Vesa Pekka Hytönen, Mataleena Parikka
Mycobacterium tuberculosis remains one of the most problematic infectious agents due to its highly developed mechanisms to evade host immune responses combined with the increasing emergence of antibiotic resistance. Host-directed therapies aiming at optimal modulation of immune responses to improve bacterial eradication or to limit excessive inflammation are a new strategy for the treatment of tuberculosis. In this study, we have established a zebrafish-Mycobacterium marinum natural host-pathogen model system to study induced protective immune responses in mycobacterial infection...
November 30, 2017: Disease Models & Mechanisms
Guoxiang Wang, Yi Ping Zhang, Zhongwen Gao, Lisa B E Shields, Fang Li, Tianci Chu, Huayi Lv, Thomas Moriarty, Xiao-Ming Xu, Xiaoyu Yang, Christopher B Shields, Jun Cai
Abusive head trauma (AHT) is the leading cause of death from trauma in infants and young children. An AHT animal model was developed on 12-day-old mice subjected to 90° head extension-flexion sagittal shaking repeated 30, 60, 80, and 100 times. The mortality and time until return of consciousness were dependent on the number of repeats and severity of the injury. Under 60 times of repeated head shakings, the pups demonstrated apnea and/or bradycardia immediately after injury. Acute oxygen desaturation was observed by pulse oximetry during respiratory and cardiac suppression...
November 30, 2017: Disease Models & Mechanisms
Aya Yoshimura, Naoki Adachi, Hitomi Matsuno, Masaki Kawamata, Yusuke Yoshioka, Hisae Kikuchi, Haruki Odaka, Tadahiro Numakawa, Hiroshi Kunugi, Takahiro Ochiya, Yoshitaka Tamai
Extracellular vesicles (EVs) can modulate microenvironments by transferring biomolecules including RNAs and proteins derived from releasing cells to target cells. To understand the molecular mechanisms maintaining the neural stem cell (NSC) niche through EVs, a new transgenic (Tg) rat strain that can release human CD63-GFP expressed EVs from the NSCs was established. Human CD63-GFP expression was controlled under the rat Sox2 promoter (Sox2/human CD63-GFP), and it was expressed in undifferentiated foetal brains...
November 30, 2017: Disease Models & Mechanisms
Ute Jungwirth, Antoinette van Weverwijk, Miriam J Melake, Ann F Chambers, Qiong Gao, Marc Fivaz, Clare M Isacke
Studying the complex mechanisms underlying breast cancer metastasis and therapy response necessitates relevant in vivo models, particularly syngeneic models with an intact immune system. Two syngeneic spontaneously metastatic sublines, D2A1-m1 and D2A1-m2, were generated from the poorly metastasising BALB/c-derived D2A1 cell line by serial in vivo passaging. In vivo and in vitro analyses revealed distinct and shared characteristics of the metastatic D2A1-m1 and D2A1-m2 sublines. In particular, D2A1-m1 cells are more aggressive in experimental metastasis assays, while D2A1-m2 cells are more efficient at disseminating from the primary tumour in spontaneous metastasis assays...
November 30, 2017: Disease Models & Mechanisms
Hatylas Azevedo, Nathália Amato Khaled, Paula Santos, Fernanda Bernardi Bertonha, Carlos Alberto Moreira-Filho
Complex febrile seizures during infancy constitute an important risk factor for epilepsy development. However, little is known about the alterations induced by febrile seizures that may turn the brain susceptible to epileptic activity. In this context, the use of animal models of hyperthermic seizures (HS) could allow the temporal analysis of brain molecular changes that arise after febrile seizures. Here, we investigated temporal changes in hippocampal gene co-expression networks during the development of rats submitted to HS...
November 30, 2017: Disease Models & Mechanisms
Jessica A Blaquiere, Kenneth Kin Lam Wong, Stephen D Kinsey, Jin Wu, Esther M Verheyen
Aberrations in signaling pathways that regulate tissue growth often lead to tumorigenesis. Homeodomain interacting protein kinase (Hipk) family members are reported to have distinct and contradictory effects on cell proliferation and tissue growth. From these studies it is clear that much remains to be learned about the roles of Hipk family protein kinases in proliferation and cell behaviour. Previous work has shown that Drosophila Hipk is a potent growth regulator, thus we predicted that it could have a role in tumorigenesis...
November 20, 2017: Disease Models & Mechanisms
Eduardo Calpena, Víctor López Del Amo, Mouli Chakraborty, Beatriz Llamusí, Rubén Artero, Carmen Espinós, Máximo I Galindo
Members of the Junctophilin (JPH) protein family have emerged as key actors in all excitable cells with critical implications for human pathophysiology. In mammals this family consists in four members (JPH1-4) that are differentially expressed throughout excitable cells. The analysis of knockout mice lacking JPH subtypes has demonstrated their essential contribution to physiological functions in skeletal and cardiac muscles, and neurons. Moreover, mutations in the human JPH2 gene are associated with hypertrophic and dilated cardiomyopathies; mutations in JPH3 are responsible for the neurodegenerative Huntington's disease-like-2 (HDL2), whereas JPH1 acts as a genetic modifier in CMT2K peripheral neuropathy...
November 20, 2017: Disease Models & Mechanisms
Qi Xu, Sanna Junttila, Andreas Scherer, Khem Raj Giri, Oona Kivelä, Ilya Skovorodkin, Juha Röning, Susan E Quaggin, Hans-Peter Marti, Jingdong Shan, Anatoly Samoylenko, Seppo J Vainio
Three-dimensional organoids provide a new way to model various diseases, including cancer. We made use of recently developed kidney organ primordia tissue engineering technologies to create novel renal organoids for cancer gene discovery. We then tested whether our novel assays can be used to examine kidney cancer development. First we identified the transcriptome profiles of quiescent embryonic metanephric mesenchymes (MM) and of MM in which the nephrogenesis program had been induced ex vivo The transcriptome profiles were then compared to the profiles of RCC patients and controls...
October 26, 2017: Disease Models & Mechanisms
Weizhe Li, Santhi Gorantla, Howard E Gendelman, Larisa Y Poluektova
Studies of innate glial cell responses for progressive human immunodeficiency virus type one (HIV-1) infection are limited by a dearth of human disease relevant small-animal models. To overcome this obstacle, newborn NOD/SCID/IL2Rγc(-/-) (NSG) mice were reconstituted with a humanized brain and immune systems. NSG animals of both sexes were transplanted with human neuroglial progenitors (NPC) and hematopoietic stem cells. Intraventricular injection of NPC symmetrically repopulated the mouse brain parenchyma with human astrocytes and oligodendrocytes...
October 26, 2017: Disease Models & Mechanisms
Rachel A Watson, Amy S Gates, Elizabeth H Wynn, Fiona E Calvert, Amandine Girousse, Christopher J Lelliott, Inês Barroso
Genome-wide association studies (GWAS) have detected association between variants in or near the Lysophospholipase-like 1 (LYPLAL1) locus and metabolic traits, including central obesity, fatty liver and waist-hip ratio. LYPLAL1 is also known to be upregulated in the adipose tissue of obese patients. However, the physiological role of LYPLAL1 is not understood. To investigate the function of Lyplal1 in vivo we investigated the phenotype of the Lyplal1(tm1a(KOMP)Wtsi) homozygous mouse. Body composition was unaltered in Lyplal1 knockout mice as assessed by Dual-energy X-ray absorptiometry (DEXA) scanning, both on normal chow and on a high fat diet...
October 26, 2017: Disease Models & Mechanisms
Vimala Kaza, Elena Farmaki, Amanda Havighorst, Janet Crossland, Ioulia Chatzistamou, Hippokratis Kiaris
Modeling breast cancer in general and hormone-sensitive breast cancer, in particular in mice, has several limitations. These are related to the inbred nature of laboratory mice, and do not allow adequate appreciation of the contribution of the host's genetic heterogeneity in tumor growth. In addition, the naturally low estrogen levels of mice makes estradiol supplementation obligatory for tumor growth. Here, we show that Peromyscus californicus, following cyclosporine-mediated immunosuppression, supports the growth of both MDA-MB-231 estrogen-independent and MCF7 estrogen receptor-positive breast cancers without exogenous estradiol supplementation...
January 17, 2018: Disease Models & Mechanisms
Ross Dobie, Vicky E MacRae, Chloe Pass, Elspeth M Milne, S Faisal Ahmed, Colin Farquharson
Individuals with inflammatory bowel disease (IBD) often present with poor bone health. The development of targeted therapies for this bone loss requires a fuller understanding of the underlying cellular mechanisms. Although bone loss in IBD is multifactorial, the altered sensitivity and secretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in IBD is understood to be a critical contributing mechanism. The expression of suppressor of cytokine signaling 2 (SOCS2), a well-established negative regulator of GH signaling, is stimulated by proinflammatory cytokines...
January 17, 2018: Disease Models & Mechanisms
Gavin Tjin, Eric S White, Alen Faiz, Delphine Sicard, Daniel J Tschumperlin, Annabelle Mahar, Eleanor P W Kable, Janette K Burgess
No abstract text is available yet for this article.
December 19, 2017: Disease Models & Mechanisms
Masayuki Nakano, Toshiya Hirayama
No abstract text is available yet for this article.
December 19, 2017: Disease Models & Mechanisms
Nicole Tegtmeyer, Steffen Backert
No abstract text is available yet for this article.
December 19, 2017: Disease Models & Mechanisms
Hong Lin, Jordi Magrane, Elisia M Clark, Sarah M Halawani, Nathan Warren, Amy Rattelle, David R Lynch
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with progressive ataxia that affects both the peripheral and central nervous system (CNS). While later CNS neuropathology involves loss of large principal neurons and glutamatergic and GABAergic synaptic terminals in the cerebellar dentate nucleus, early pathological changes in FRDA cerebellum remain largely uncharacterized. Here, we report early cerebellar VGLUT1 (SLC17A7)-specific parallel fiber (PF) synaptic deficits and dysregulated cerebellar circuit in the frataxin knock-in/knockout (KIKO) FRDA mouse model...
December 19, 2017: Disease Models & Mechanisms
Kristin Eden, Daniel E Rothschild, Dylan K McDaniel, Bettina Heid, Irving C Allen
Eosinophilic esophagitis (EoE) is an allergic disease of the esophagus driven by T cell and eosinophil responses to dietary allergens, resulting in chronic mucosal inflammation. Few spontaneous animal models of esophageal eosinophilia exist, with most studies relying on artificial sensitization procedures. NF-κB-inducing kinase (NIK; MAP3K14) is a key signaling molecule of the noncanonical NF-κB (NFKB1) pathway, an alternative signaling cascade producing chemokines involved in lymphoid stroma development and leukocyte trafficking...
December 19, 2017: Disease Models & Mechanisms
Héctor Fernández-Susavila, Ramón Iglesias-Rey, Antonio Dopico-López, María Pérez-Mato, Tomás Sobrino, José Castillo, Francisco Campos
Proper occlusion of the medial cerebral artery, as determined by laser Doppler monitoring, during cerebral ischaemia in rat models is an important inclusion criterion in experimental studies. However, successful occlusion of the artery does not always guarantee a reproducible infarct volume, which is crucial for validating the efficacy of new protective drugs. In a rat intraluminal ischaemic model, laser Doppler monitoring alone was compared with laser Doppler monitoring in combination with magnetic resonance angiography (MRA) and diffusion-weighted imaging (DWI)...
December 19, 2017: Disease Models & Mechanisms
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