Maximizing mouse cancer models
19 important questions on Maximizing mouse cancer models
What are Genetically engineered mice?
(GEM). Mice harbouring genetic modifications designed to express either exogenous or endogenous mutated genes. In cancer modelling, these are frequently oncogenes or tumour-suppressor genes.
What is Cell autonomous?
A trait engendered only in cells harbouring the mutation. In the case of a carcinoma, a cell autonomous function occurs only in the mutant tumour epithelial cells.
What is Non-cell autonomous?
A trait engendered in cells that do not harbour the mutation. In the case of a carcinoma, a non-cell autonomous function occurs in stromal, immune and endothelial cells.
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What is one of the best model systems for investigations of cancer biology in vivo?
The laboratory mouse (Mus musculus) is one of the best model systems for investigations of cancer biology in vivo, ranging from basic models such as xenograft tumours derived from tumour cell lines or explants, to highly complex
genetically engineered mice (GEM).
What is a good way to describe a xenograft?
Xenografts represent an intermediate step between cell culture and mouse cancer models, and could be more accurately termed ‘animal culture’.
How can GEM be classified?
GEM can be classified as either transgenic or endogenous. This distinction is not merely semantic but is highly relevant, because the type of GEM can determine the experimental outcome in certain situations.
Transgenic GEM are mutant mice that express oncogenes or dominant-negative tumour-suppressor genes (TSGs) in a non-physiological manner owing to ectopic promoter and enhancer elements. What are the advantages, and name a disadvantage.
Advantages of transgenic GEM include the ability to reversibly control target-gene expression with exogenous ligands. One disadvantage is that it might be difficult to elicit the exquisite control necessary to express oncogenes at physiological levels.
What are modern GEM for?
Modern GEM are poised to explore facets of cancer biology and medicine that are difficult or impossible to pursue clinically. However, all GEM described so far have certain shortcomings in mimicking human malignancy. Several issues (such as humanizing mice) and practical considerations concerning GEM will need to be addressed in order to meet our objectives.
What is an Autochthonous tumour?
An endogenous or in situ tumour that evolves from normal cells of a tumourbearing animal. This is in contrast to animal cultures in which exogenous tumour cells are implanted into a nontumour- bearing animal.
What is the meaning of the term Tumour microenvironment?
The stroma and supporting milieu surrounding the tumour that consists of fibroblasts, immune cells and endothelial
cells.
What is Oncogene addiction?
The hypothesis that tumours arising as a result of a particular oncogenic lesion are exquisitely dependent on continued expression of that oncogene.
What are Conditional models?
GEM that rely on site-specific recombinase systems to engender gene expression in a spatially and/or temporally restricted manner.
What is Site-specific recombinase?
(SSR). An enzyme, such as bacterial Cre, that catalyses recombination between two specific inverted repeat sequences (such as LoxP).
What is a latent allele?
An endogenous GEM strategy in which a stochastic recombination event is required to activate expression of the oncogenic allele. This is one of the few endogenous GEM that does not require a site-specific recombinase.
What is a Hypomorphic allele?
A mutation conveying decreased activity, either through reduced expression or partial loss of function.
What is a Neomorphic allele?
A mutation conveying a novel activity not present in the wild type protein.
What is a Adeno-associated virus?
(AAV) Small DNA viruses often used for gene therapy due to their broad host range and the ability to infect non-dividing cells.
What are Xenobiotic receptors?
A family of enzymes involved in the metabolism of drugs by sensing the presence of a drug and initiating a response.
What is Cytochrome P450?
A family of metabolic enzymes responsible for detoxifying and modifying drugs and other foreign compounds.
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