scholarly journals Identification of genes escaping X inactivation by allelic expression analysis in a novel hybrid mouse model

Data in Brief ◽  
2015 ◽  
Vol 5 ◽  
pp. 761-769 ◽  
Author(s):  
Joel B. Berletch ◽  
Wenxiu Ma ◽  
Fan Yang ◽  
Jay Shendure ◽  
William S. Noble ◽  
...  
Keyword(s):  
Mouse Model ◽  
Expression Analysis ◽  
X Inactivation ◽  
Allelic Expression ◽  
Hybrid Mouse

scholarly journals Gene Expression Analysis of the Activating Factor 3/Nuclear Protein 1 Axis in a Non-alcoholic Steatohepatitis Mouse Model

2019 ◽  
Vol 62 (1) ◽  
pp. 036-046 ◽  
Author(s):  
Ran Nagahara ◽  
Tomomitsu Matono ◽  
Takaaki Sugihara ◽  
Yukako Matsuki ◽  
Masafumi Yamane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Nuclear Protein ◽  
Alcoholic Steatohepatitis

scholarly journals Allelic expression analysis of the osteoarthritis susceptibility locus that maps to MICAL3

2012 ◽  
Vol 13 (1) ◽  
Author(s):  
Madhushika Ratnayake ◽  
Louise N Reynard ◽  
Emma VA Raine ◽  
Mauro Santibanez-Koref ◽  
John Loughlin
Keyword(s):  
Expression Analysis ◽  
Allelic Expression ◽  
Susceptibility Locus

scholarly journals A Novel Susceptibility Locus On Chromosome 2 in the (New Zealand Black × New Zealand White)F1 Hybrid Mouse Model of Systemic Lupus Erythematosus

2002 ◽  
Vol 168 (6) ◽  
pp. 3042-3049 ◽  
Author(s):  
Ziaur SM. Rahman ◽  
Soe-Kyaw Tin ◽  
Pia-Nina L. Buenaventura ◽  
Chiu-Han Ho ◽  
Eric P. H. Yap ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
New Zealand ◽  
Mouse Model ◽  
Lupus Erythematosus ◽  
Susceptibility Locus ◽  
Chromosome 2 ◽  
Systemic Lupus ◽  
F1 Hybrid ◽  
Hybrid Mouse

Mechanisms of Relapse Following Targeted Therapy in An NRASG12V and Mll-AF9 Driven Mouse Model of AML

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2620-2620
Author(s):  
Craig E. Eckfeldt ◽  
Ernesto Diaz-Flores ◽  
Michaeleen D. Diers ◽  
Susan K. Rathe ◽  
Kevin M. Shannon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Expression Analysis ◽  
Targeted Therapies ◽  
Expression Profiles ◽  
Critical Role ◽  
Negative Regulator ◽  
Erk Signaling ◽  
Genetic Mutations ◽  
Ras Signaling ◽  
Equity Ownership

Abstract Abstract 2620 Acute Myeloid Leukemia (AML) is driven by genetic mutations that promote proliferation and prevent maturation of myeloid progenitors. While the majority of adults with AML achieve a remission with aggressive cytotoxic chemotherapy, a large proportion will ultimately die of relapsed/refractory disease. Given the limited efficacy and significant toxicity associated with current AML treatment strategies, new therapies are needed. While many genetic mutations have been shown to contribute to the development AML, the genetic heterogeneity seen in AML presents a challenge for the development of targeted therapies. The NRAS proto-oncogene and other key mediators of RAS signaling are frequently mutated in AML, making RAS-targeted therapies an attractive strategy for the treatment of AML. We previously developed an in vivo genetically-engineered mouse (GEM) model of AML driven by a tetracycline-repressible, constitutively-active form of NRAS, NRASG12V, and the leukemogenic fusion gene Mll-AF9. The leukemia cells in this model are “addicted” to NRASG12V, and inhibiting its expression with doxycycline (dox) results in rapid, complete remission of the AML. However, we have found that some mice relapse with NRASG12V-independent “dox-resistant” disease after continued suppression of NRASG12V expression, a phenomenon we might expect to occur in human AML after Ras signal pathway inhibition. To investigate the mechanisms of relapse in this model we generated two NRASG12V-independent (NRI) AML clones from a single primary NRASG12V-dependent (NRD) AML. We performed Affymetrix-based global gene expression analysis to compare the expression profiles of the primary NRD AML with the relapsed NRI AMLs. We identified 79 genes that were expressed at ≥ 2-fold higher levels in the NRD AML compared to both NRI AMLs. Among these were the putative tumor suppressor Cav2, and a negative regulator of Ras/Raf/Mek/Erk signaling, Dusp6. Down regulation of Dusp6 could enhance Raf/Mek/Erk signaling in the absence of NRASG12V, and thereby circumvent “addiction” to NRASG12V. Expression analysis also identified 20 genes that were expressed at ≥ 2-fold higher levels in both relapsed NRI AMLs compared to the primary NRD AML. Interestingly a Myc oncogene family member, Mycn (N-Myc), was expressed at > 60-fold higher levels in relapsed NRI AMLs compared to the primary NRD AML. Enforced expression of Mycn is sufficient to give rise to AML in a mouse model, and MYCN is widely expressed in human AML (Kawagoe et al. Cancer Res. 2007;67:10677), suggesting a critical role for Mycn in the development of relapsed NRI AML in this model. We are in the process of investigating whether enforced expression of Mycn and/or loss of Dusp6 are sufficient for the development of resistant NRI AML, and conversely if loss of Mycn and/or enforced expression of Dusp6 restore NRASG12V dependence in this model. We are also performing multi-parameter phosho-flow cytometery to further elucidate the mechanisms of AML resistance and relapse and to identify potentially “druggable” targets for AML. This represents an important step toward understanding the genetic determinates of treatment response and disease relapse with Ras pathway targeted therapies for AML, and thus provides a foundation for developing more effective and less toxic therapies for AML. Disclosures: Largaespada: NeoClone Biotechnology, Inc.: Co-founder, Consultancy, Equity Ownership; Discovery Genomics Inc.: Co-founder, Consultancy, Equity Ownership.

scholarly journals Tools and best practices for data processing in allelic expression analysis

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Stephane E. Castel ◽  
Ami Levy-Moonshine ◽  
Pejman Mohammadi ◽  
Eric Banks ◽  
Tuuli Lappalainen
Keyword(s):  
Best Practices ◽  
Data Processing ◽  
Expression Analysis ◽  
Allelic Expression
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