scholarly journals Prostate Pathology of Genetically Engineered Mice: Definitions and Classification. The Consensus Report from the Bar Harbor Meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee

2004 ◽  
Vol 64 (6) ◽  
pp. 2270-2305 ◽  
Author(s):  
Scott B. Shappell ◽  
George V. Thomas ◽  
Richard L. Roberts ◽  
Ron Herbert ◽  
Michael M. Ittmann ◽  
...  
Keyword(s):  
Mouse Models ◽  
Human Cancer ◽  
Genetically Engineered ◽  
Genetically Engineered Mice ◽  
Consensus Report

scholarly journals Genetically engineered ERα-positive breast cancer mouse models

2014 ◽  
Vol 21 (3) ◽  
pp. R195-R208 ◽  
Author(s):  
Sarah A Dabydeen ◽  
Priscilla A Furth
Keyword(s):  
Mouse Models ◽  
Mammary Cancer ◽  
Human Cancer ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genetically Engineered ◽  
Spontaneous Mutant ◽  
Breast Cancers ◽  
Pparγ Agonist ◽  
Genetically Engineered Mice

The majority of human breast cancers are estrogen receptor-positive (ER+), but this has proven challenging to model in genetically engineered mice. This review summarizes information on 21 mouse models that develop ER+ mammary cancer. Where available, information on cancer pathology and gene expression profiles is referenced to assist in understanding which histological subtype of ER+ human cancer each model might represent.ESR1,CCDN1, prolactin,TGFα,AIB1,ESPL1, andWNT1overexpression,PIK3CAgain of function, as well as loss ofP53(Trp53) orSTAT1are associated with ER+ mammary cancer. Treatment with the PPARγ agonist efatutazone in a mouse withBrca1andp53deficiency and 7,12-dimethylbenz(a)anthracene exposure in combination with an activated myristoylated form of AKT1 also induce ER+ mammary cancer. A spontaneous mutant in nude mice that develops metastatic ER+ mammary cancer is included. Age of cancer development ranges from 3 to 26 months and the percentage of cancers that are ER+ vary from 21 to 100%. Not all models are characterized as to their estrogen dependency and/or response to anti-hormonal therapy. Strain backgrounds include C57Bl/6, FVB, BALB/c, 129S6/SvEv, CB6F1, and NIH nude. Most models have only been studied on one strain background. In summary, while a range of models are available for studies of pathogenesis and therapy of ER+ breast cancers, many could benefit from further characterization, and opportunity for development of new models remains.

scholarly journals Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma

2016 ◽  
Vol 113 (42) ◽  
pp. E6409-E6417 ◽  
Author(s):  
David G. McFadden ◽  
Katerina Politi ◽  
Arjun Bhutkar ◽  
Frances K. Chen ◽  
Xiaoling Song ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mouse Models ◽  
Cancer Progression ◽  
Large Scale ◽  
Human Cancer ◽  
Genetically Engineered ◽  
Model Systems ◽  
Driver Mutations ◽  
Genetic Profile ◽  
Genetically Engineered Mouse Models

Genetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC proto-oncogene. Tumors from EGFR- and Kras-driven models exhibited, respectively, 0.02 and 0.07 nonsynonymous mutations per megabase, a dramatically lower average mutational frequency than observed in human lung adenocarcinomas. Tumors from models driven by strong cancer drivers (mutant EGFR and Kras) harbored few mutations in known cancer genes, whereas tumors driven by MYC, a weaker initiating oncogene in the murine lung, acquired recurrent clonal oncogenic Kras mutations. In addition, although EGFR- and Kras-driven models both exhibited recurrent whole-chromosome DNA copy number alterations, the specific chromosomes altered by gain or loss were different in each model. These data demonstrate that GEMM tumors exhibit relatively simple somatic genotypes compared with human cancers of a similar type, making these autochthonous model systems useful for additive engineering approaches to assess the potential of novel mutations on tumorigenesis, cancer progression, and drug sensitivity.

scholarly journals Mouse models for BRAF-induced cancers

2007 ◽  
Vol 35 (5) ◽  
pp. 1329-1333 ◽  
Author(s):  
C. Pritchard ◽  
L. Carragher ◽  
V. Aldridge ◽  
S. Giblett ◽  
H. Jin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Models ◽  
Human Cancer ◽  
Cre Recombinase ◽  
Genetically Engineered ◽  
Mitogen Activated Protein Kinase ◽  
Braf Mutations ◽  
Single Nucleotide Change

Oncogenic mutations in the BRAF gene are detected in ∼7% of human cancer samples with a particularly high frequency of mutation in malignant melanomas. Over 40 different missense BRAF mutations have been found, but the vast majority (>90%) represent a single nucleotide change resulting in a valine→glutamate mutation at residue 600 (V600EBRAF). In cells cultured in vitro, V600EBRAF is able to stimulate endogenous MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] and ERK phosphorylation leading to an increase in cell proliferation, cell survival, transformation, tumorigenicity, invasion and vascular development. Many of these hallmarks of cancer can be reversed by treatment of cells with siRNA (small interfering RNA) to BRAF or by inhibiting MEK, indicating that BRAF and MEK are attractive therapeutic targets in cancer samples with BRAF mutations. In order to fully understand the role of oncogenic BRAF in cancer development in vivo as well as to test the in vivo efficacy of anti-BRAF or anti-MEK therapies, GEMMs (genetically engineered mouse models) have been generated in which expression of oncogenic BRaf is conditionally dependent on the Cre recombinase. The delivery/activation of the Cre recombinase can be regulated in both a temporal and spatial manner and therefore these mouse models can be used to recapitulate the somatic mutation of BRAF that occurs in different tissues in the development of human cancer. The data so far obtained following Cre-mediated activation in haemopoietic tissue and the lung indicate that V600EBRAF mutation can drive tumour initiation and that its primary effect is to induce high levels of cyclin D1-mediated cell proliferation. However, hallmarks of OIS (oncogene-induced senescence) are evident that restrain further development of the tumour.

scholarly journals Pathology of Genetically Engineered Mouse Models of Pancreatic Exocrine Cancer: Consensus Report and Recommendations

2006 ◽  
Vol 66 (1) ◽  
pp. 95-106 ◽  
Author(s):  
Ralph H. Hruban ◽  
N. Volkan Adsay ◽  
Jorge Albores-Saavedra ◽  
Miriam R. Anver ◽  
Andrew V. Biankin ◽  
...  
Keyword(s):  
Mouse Models ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models ◽  
Pancreatic Exocrine ◽  
Consensus Report

Factor IX: Insights from knock-out and genetically engineered mice

2008 ◽  
Vol 100 (10) ◽  
pp. 563-575 ◽  
Author(s):  
Paul E. Monahan
Keyword(s):  
Mouse Models ◽  
Positional Cloning ◽  
Coagulation Factors ◽  
Genetically Engineered ◽  
Factor Ix ◽  
Mouse Strains ◽  
Knock Out ◽  
Haemophilia B ◽  
Genetically Engineered Mice ◽  
Knock Out Mice

SummaryThe study of coagulation factors has been rapidly advanced by studies performed in genetically engineered mouse strains. Investigation of factor IX (FIX) has benefited from excellent genedeleted mouse models that recapitulate many of the features of human haemophilia B. Moreover, advanced positional cloning techniques and availability of technology to allow not only knock-out mice, but also knock-in and knock-down mice, provide new opportunities to observe genotype-phenotype and structure-function correlations regarding FIX, as well as the interaction of FIX with inflammatory, immune, and tissue repair systems. In this paper, available FIX knock-out mice and additional haemophilia B mouse models are reviewed specifically in regards to observations these models have facilitated concerning: factor IX gene expression and factor IX protein pharmacokinetics; the role of FIX in haemostasis, thrombosis and wound healing; insights into coagulation FIX arising out of gene therapy applications in haemophilia mouse models; immunology of tolerance or loss of tolerance of FIX and inhibitor antibody formation.

scholarly journals How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancers

2011 ◽  
Vol 29 (16) ◽  
pp. 2273-2281 ◽  
Author(s):  
Katerina Politi ◽  
William Pao
Keyword(s):  
Mouse Models ◽  
Cancer Biology ◽  
Human Cancer ◽  
Genetically Engineered ◽  
Mouse Tumor ◽  
Tumor Models ◽  
Genetically Engineered Mouse Models ◽  
Human Cancers ◽  
Chemically Induced

Genetically engineered mouse models (GEMMs) of human cancer were first created nearly 30 years ago. These early transgenic models demonstrated that mouse cells could be transformed in vivo by expression of an oncogene. A new field emerged, dedicated to generating and using mouse models of human cancer to address a wide variety of questions in cancer biology. The aim of this review is to highlight the contributions of mouse models to the diagnosis and treatment of human cancers. Because of the breadth of the topic, we have selected representative examples of how GEMMs are clinically relevant rather than provided an exhaustive list of experiments. Today, as detailed here, sophisticated mouse models are being created to study many aspects of cancer biology, including but not limited to mechanisms of sensitivity and resistance to drug treatment, oncogene cooperation, early detection, and metastasis. Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review.

scholarly journals Biochemical and Functional Comparisons ofmdxandSgcg−/−Muscular Dystrophy Mouse Models

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Nathan W. Roberts ◽  
Jenan Holley-Cuthrell ◽  
Magdalis Gonzalez-Vega ◽  
Aaron J. Mull ◽  
Ahlke Heydemann
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Models ◽  
Time Course ◽  
Genetically Engineered ◽  
Blue Dye ◽  
Null Mouse ◽  
Human Genetic Disease ◽  
Mild Disease ◽  
Diagnosis And Prognosis ◽  
Genetically Engineered Mice

Mouse models have provided an essential platform to investigate facets of human diseases, from etiology, diagnosis, and prognosis, to potential treatments. Muscular dystrophy (MD) is the most common human genetic disease occurring in approximately 1 in 2500 births. Themdxmouse, which is dystrophin-deficient, has long been used to model this disease. However, this mouse strain displays a rather mild disease course compared to human patients. Themdxmice have been bred to additional genetically engineered mice to worsen the disease. Alternatively, other genes which cause human MD have been genetically disrupted in mice. We are now comparing disease progression from one of these alternative gene disruptions, theγ-sarcoglycan null mouseSgcg−/−on the DBA2/J background, to themdxmouse line. This paper aims to assess the time-course severity of the disease in the mouse models and determine which is best for MD research. TheSgcg−/−mice have a more severe phenotype than themdxmice. Muscle function was assessed by plethysmography and echocardiography. Histologically theSgcg−/−mice displayed increased fibrosis and variable fiber size. By quantitative Evan’s blue dye uptake and hydroxyproline content two key disease determinants, membrane permeability and fibrosis respectively, were also proven worse in theSgcg−/−mice.

scholarly journals The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting

Oncogene ◽  
2000 ◽  
Vol 19 (8) ◽  
pp. 968-988 ◽  
Author(s):  
Robert D Cardiff ◽  
Miriam R Anver ◽  
Barry A Gusterson ◽  
Lothar Hennighausen ◽  
Roy A Jensen ◽  
...  
Keyword(s):  
Genetically Engineered ◽  
Genetically Engineered Mice ◽  
Consensus Report

scholarly journals Laboratory Mice – A Driving Force in Immunopathology and Immunotherapy Studies of Human Multiple Myeloma

2021 ◽  
Vol 12 ◽  
Author(s):  
Michael Pisano ◽  
Yan Cheng ◽  
Fumou Sun ◽  
Binod Dhakal ◽  
Anita D’Souza ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Mouse Models ◽  
Plasma Cell ◽  
Plasma Cells ◽  
De Novo ◽  
Human Cancer ◽  
Tumor Development ◽  
Adaptive Immune Response ◽  
Genetically Engineered

Mouse models of human cancer provide an important research tool for elucidating the natural history of neoplastic growth and developing new treatment and prevention approaches. This is particularly true for multiple myeloma (MM), a common and largely incurable neoplasm of post-germinal center, immunoglobulin-producing B lymphocytes, called plasma cells, that reside in the hematopoietic bone marrow (BM) and cause osteolytic lesions and kidney failure among other forms of end-organ damage. The most widely used mouse models used to aid drug and immunotherapy development rely on in vivo propagation of human myeloma cells in immunodeficient hosts (xenografting) or myeloma-like mouse plasma cells in immunocompetent hosts (autografting). Both strategies have made and continue to make valuable contributions to preclinical myeloma, including immune research, yet are ill-suited for studies on tumor development (oncogenesis). Genetically engineered mouse models (GEMMs), such as the widely known Vκ*MYC, may overcome this shortcoming because plasma cell tumors (PCTs) develop de novo (spontaneously) in a highly predictable fashion and accurately recapitulate many hallmarks of human myeloma. Moreover, PCTs arise in an intact organism able to mount a complete innate and adaptive immune response and tumor development reproduces the natural course of human myelomagenesis, beginning with monoclonal gammopathy of undetermined significance (MGUS), progressing to smoldering myeloma (SMM), and eventually transitioning to frank neoplasia. Here we review the utility of transplantation-based and transgenic mouse models of human MM for research on immunopathology and -therapy of plasma cell malignancies, discuss strengths and weaknesses of different experimental approaches, and outline opportunities for closing knowledge gaps, improving the outcome of patients with myeloma, and working towards a cure.

Sign in / Sign up

Export Citation Format

Share Document