Mouse model of paraquat-poisoned lungs and its gene expression profile

Toxicology ◽  
2007 ◽  
Vol 231 (2-3) ◽  
pp. 200-209 ◽  
Author(s):  
M TOMITA ◽  
T OKUYAMA ◽  
H KATSUYAMA ◽  
Y MIURA ◽  
Y NISHIMURA ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Its Gene

scholarly journals The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

2014 ◽  
Vol 19 (4) ◽  
Author(s):  
Patricia Sanz-Ramos ◽  
Javier Dotor ◽  
Iñigo Izal-Azcárate
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Peptide Inhibitors ◽  
Mechanical Environment ◽  
Chondrocyte Phenotype ◽  
Cartilage Cells ◽  
Alk 5

AbstractWe aim to demonstrate the role of Alk receptors in the response of hydrogel expansion. Chondrocytes from rat knees were cultured onto plastic and hydrogel surfaces. Alk-1 and Alk-5 were overexpressed or silenced and the effects on cells during expansion were tested and confirmed using peptide inhibitors for TGFβ. Overexpression of Alk-5 and silencing of Alk-1 led to a loss of the chondrocyte phenotype, proving that they are key regulators of chondrocyte mechanosensing. An analysis of the gene expression profile during the expansion of these modified cartilage cells in plastic showed a better maintenance of the chondrocyte phenotype, at least during the first passages. These passages were also assayed in a mouse model of intramuscular chondrogenesis. Our findings indicate that these two receptors are important mediators in the response of chondrocytes to changes in the mechanical environment, making them suitable targets for modulating chondrogenesis. Inhibition of TGFβ could also be effective in improving chondrocyte activity in aged or expanded cells that overexpress Alk-1.

A Serial Analysis of Gene Expression Profile of the Alzheimer’s Disease Tg2576 Mouse Model

2009 ◽  
Vol 17 (4) ◽  
pp. 360-379 ◽  
Author(s):  
Amee J. George ◽  
Lavinia Gordon ◽  
Tim Beissbarth ◽  
Irene Koukoulas ◽  
R. M. Damian Holsinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Tg2576 Mouse

Gene Expression Profile of Acute Myeloid Leukemia (AML) with t(8;16)(p11;p13) and MYST3/CREBBP Rearrangement.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2054-2054
Author(s):  
Mireia Camos ◽  
Jordi Esteve ◽  
Pedro Jares ◽  
Maria Rozman ◽  
Dolors Colomer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
De Novo ◽  
Normal Karyotype ◽  
Genetic Profile ◽  
Transferase Activity ◽  
Internal Tandem Duplication ◽  
Its Gene ◽  
Differential Expression Profile

Abstract Translocation t(8;16)(p11;p13) is an infrequent chromosomal abnormality in de novo and secondary AML cases, leading to the fusion of MYST3 (MOZ) and CREBBP (CBP) genes, both of them harboring histone lysine acetyl-transferase activity. This AML variety displays specific clinical and biological features, although its gene expression profile is currently unknown. In this study, the genetic signature of AML cases with MYST3/CREBBP rearrangement was compared with the genetic profile of other well-defined AML subtypes. Genotypic analyses using oligonucleotide U133A arrays (Affymetrix) were performed on RNA of 19 AML samples, including t(8;16)-AML (n=3), t(15;17) (n=3), t(8;21) (n=2), inv(16)/t(16;16) (n=3), t(9;11) with AF9/MLL rearrangement (n=2), 3 cases with normal karyotype and flt-3 internal tandem duplication (flt-3 ITD), the three remaining samples corresponding to monocytic cases (M4/M5) without MLL rearrangement nor flt-3 ITD. After unsupervised analysis, cases of AML with t(8;16) clustered together, displaying a differential expression profile. Supervised analysis allowed the identification of the top 53 up-regulated and 28 down-regulated genes. Among the set of genes overexpressed, genes involved in chromatin remodelling and transcription (HOXA9, HOXA10, MEIS1, CHD3, SATB1) and protooncogenes (RET, flt-3, LMO2) were identified. In contrast, CREBBP gene and several members of the JAK-STAT pathway (STAT3, STAT5B, JAK2) were underexpressed. Interestingly, overexpression of multiple homeobox genes was detected in flt-3 ITD cases, some of them as a distinctive finding (HOXA2, HOXA3, HOXB6), and others (HOXA9, HOXA10, MEIS1) were found to be highly expressed in MYST3/CREBBP and MLL-rearranged samples. In conclusion, AML with t(8;16) and MYST3/CREBBP rearrangement shows a distinctive gene expression profile, with some similarities with MLL rearranged leukemias and flt-3 ITD AML cases, thus suggesting a partially common leukemogenic pathway.

scholarly journals Altered gene expression profile in a mouse model of SCN8A encephalopathy

2017 ◽  
Vol 288 ◽  
pp. 134-141 ◽  
Author(s):  
Ryan S. Sprissler ◽  
Jacy L. Wagnon ◽  
Rosie K. Bunton-Stasyshyn ◽  
Miriam H. Meisler ◽  
Michael F. Hammer
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Altered Gene Expression ◽  
Altered Gene

scholarly journals The Krüppel-like Factor 4 Sustains a Leukemic Gene Expression Profile in MLL-AF9-Driven Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1143-1143
Author(s):  
Andrew Lewis ◽  
Cory Seth Bridges ◽  
David Moorshead ◽  
Wa Du ◽  
Barry Zorman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Mouse Model ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Myeloid Leukemia ◽  
Ras Signaling ◽  
Targeted Deletion ◽  
Syngeneic Mouse Model ◽  
Acute Myeloid

Abstract Among hematological malignancies, acute myeloid leukemia (AML) confers poor prognosis and limited progress has been made in the translation of decades of research into improved clinical outcomes. The current paradigm is that eradication of leukemia stem cells (LSCs) represents an avenue for overcoming relapse and refractory disease, but therapy focusing on eradicating this leukemic population has not been developed to-date. Further studies of unique signaling pathways and vulnerabilities in LSCs are warranted to design targeted therapies that could impact patient outcomes. To evaluate whether the stemness transcription factor Krüppel-like Factor 4 (KLF4) is important in the progression of AML, we retrovirally transduced MLL-AF9 into Klf4 fl/fl(fl/fl)and Klf4 fl/flVav-Cre (Δ/Δ) lineage − Sca-1 + c-Kit + (LSK) bone marrow cells and transplanted into C57BL/6 recipients. Here we report that the KLF4 promotes disease progression in the MLL-AF9-driven syngeneic AML mouse model. Strikingly, Δ/Δ AMLs exhibited improved disease latency and penetrance, and a seven-fold reduction in leukemia-initiating cell frequency in a secondary transplantation study. Δ/Δ LSCs, defined as leukemic granulocyte macrophage progenitors (L-GMP), demonstrated lessened clonogenicity in methylcellulose cultures and reduced representation of cells in the G 2/M phase of the cell cycle. RNAseq analysis of L-GMP revealed decreased expression of hematopoietic and leukemic stemness gene sets such as RAS signaling, and induction of inflammatory response gene (TNF-α, IFNα, IFNβ) pathways in Δ/Δ LSCs. To evaluate human relevance, we used CRISPR-Cas9 based targeted deletion of the human KLF4 gene in a MLL-AF9 PDX line and observed improved survival and defects in expansion as seen in the syngeneic mouse model . Lastly, to correlate KLF4-associated signaling present in murine AML LSCs with human AML, we used CRISPR-Cas9-based targeted deletion of KLF4 in MOLM-13 (KO) to generate two validated clones. MOLM-13 KO cells showed reduced cell proliferation in vitro and in vivo. Further, RPPA analysis revealed reduced RAS pathway activity (IR-β, β-Raf), accumulation of proteins associated with the S and G 1 phases (e.g., CDKN2A, p21, Histone H3, CENP-A), and decrease expression in regulators of the G 2/M checkpoint (e.g., Aurora A, B, Chk1, Plk1, Wee1, Cyclin B, pCDK1). Collectively, our data suggest a mechanism in which KLF4 contributes to AML disease by establishing a gene expression profile supporting stemness of AML LSCs. Disclosures No relevant conflicts of interest to declare.

Gene expression profile in mouse model of myocardial ischemia

1999 ◽  
Vol 5 (3) ◽  
pp. 22
Author(s):  
Deborah Lyn ◽  
Xiaowei Liu ◽  
Nicole A. Bennett ◽  
Nerimiah L. Emmett
Keyword(s):  
Gene Expression ◽  
Myocardial Ischemia ◽  
Mouse Model ◽  
Gene Expression Profile ◽  
Expression Profile
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