Animal Models Flashcards
Describe the advantages of using animal models in studying human disease.
Animal models are less ethically controversial and practically simpler than research in humans, making them useful tools for studying human disease.
List the five most commonly used animal models for studying human disease.
The five commonly used animal models are budding yeast, C. elegans, D. melanogaster, zebrafish, and mice.
Define budding yeast and its relevance in research.
Budding yeast are single-cell eukaryotes that have transcription and translation processes similar to humans, making them useful for studying gene roles.
How do D. melanogaster contribute to the study of neurological disorders?
D. melanogaster (fruit flies) are beneficial for studying neurological disorders because their behavior can be observed quickly compared to mice.
Explain the significance of C. elegans in genetic research.
C. elegans (worms) have nerves and muscles similar to humans and possess polytene chromosomes, which are useful for gene mapping.
What are the advantages of using zebrafish in research?
Zebrafish are transparent, allowing for easy observation, and they have a fast and inexpensive generation time.
Describe the unique feature of frogs at the two-cell stage in research.
At the two-cell stage, frogs do not have communication between cells, allowing one side to serve as a control for the other.
How do mice serve as models for studying human disease?
Mice are vertebrates with circulation similar to humans, and their inbred genetics provide a more uniform genetic background for research.
Differentiate between transgenic and knockout models in research.
Transgenic models involve the over-expression of a gene, while knockout models involve the deletion of a gene to study its effects.
In what situations would transgenic mice be used in research?
Transgenic mice are used when researchers want to study the effects of over-expressing a specific gene, often including its own enhancer and promoter.
Describe the purpose of knockout mice in genetic studies.
Knockout mice are used to study loss of function mutations by creating a targeted gene mutation that removes the active exon of a gene.
How are knockout mice developed?
Knockout mice are developed by creating a gene construct of the targeted gene with the active exon removed, which is then inserted into the germline endogenous DNA through homologous recombination.
Define transgenic mice and their significance in research.
Transgenic mice are genetically modified mice that carry foreign DNA integrated into their genome, allowing researchers to study the effects of specific genes and diseases.
Explain the process of creating transgenic mice.
Transgenic mice are created by injecting a solution of DNA into the nucleus of a fertilized mouse egg, which is then transferred to a foster female mouse, allowing the foreign DNA to be passed on to offspring.
How do transgenic and knockout models differ in their genetic modifications?
Transgenic models involve the introduction of foreign DNA, while knockout models involve the targeted mutation or removal of an existing gene.
Name a disease studied using transgenic mice and summarize the findings.
Transgenic mice have been used to study Huntington’s Disease, revealing insights into the effects of CAG repeat mutations.
Describe the findings from studies using knockout mice related to serotonin.
Studies using knockout mice have shown that both excessive and greatly reduced levels of serotonin can lead to aggressive behavior in mice.
What is the role of germ cells in the creation of transgenic and knockout mice?
Genetic changes must occur in the germ cells to ensure that the modifications can be passed on to the progeny.
How successful is the integration of foreign DNA in transgenic mice?
About 10–20% of the offspring of transgenic mice will carry the new gene after the DNA integrates into the chromosomes during early development.
Describe the process for making knockout mice.
Knockout mice are developed by creating a gene construct of the targeted gene with the active exon removed. This construct is inserted into the germline endogenous DNA, where it ideally undergoes homologous recombination to knock out the active exon.
How can cell-type-specific knockout mice be created?
Cell-type-specific knockout mice are created by using promoters that are only found in specific cells, allowing for the knockout of genes that have differential functional activity in those specific cells.
Define a limitation of knockout mice technology.
One limitation of knockout mice technology is that it is not possible to create knockouts of genes that are essential for survival.
What is the role of positive selection in the creation of knockout mice?
Positive selection involves using an antibiotic resistance gene, such as the neomycin resistance gene, to select for cells that have successfully integrated the knockout construct.
Explain the concept of negative selection in the context of knockout mice.
Negative selection involves using a method, such as HSV, to eliminate cells that have not undergone the desired genetic modification, ensuring that only successfully modified cells are retained.
Describe the characteristics of spontaneous mouse models.
Spontaneous mouse models, such as the Jackson Labs obese mouse, are naturally occurring and can exhibit traits like being twice the size of regular mice.
What are the three types of mouse models?
The three types of mouse models are spontaneous, induced, and genetically modified.
How do Cre Lox mice function in genetic research?
Cre Lox mice allow for conditional changes in gene expression, enabling researchers to knock out or knock in genes in specific areas of the body.
Define the CRISPR technology in genetic modification.
CRISPR technology uses guide RNA to match a DNA sequence and bring the Cas9 enzyme to cut it, allowing for gene knock-ins or knock-outs.
What are the potential drawbacks of using CRISPR technology?
The potential drawbacks of using CRISPR technology include off-target effects and random DNA breaks, which could be dangerous in humans.
What are the advantages of CRISPR technology?
CRISPR technology may be cheaper and faster compared to traditional genetic modification methods.
Describe the advantages of using mice as animal models for human disease.
Mice are inexpensive, have a short lifespan making them practical for studies, and are mammals with similar physiology and development to humans. They are also social, curious, and resourceful.
Identify the limitations of using mice as models for human behavior.
Mice do not reflect human behavior accurately due to their less developed brains, raising questions about their motivations, feelings, and emotions.
Explain the significance of using a knockout mouse model for studying cystic fibrosis.
A knockout model is appropriate for studying cystic fibrosis because it focuses on loss of function mutations, which is relevant to the disease’s mechanism.
How does going germline affect the creation of transgenic mouse models?
Mice must go germline to ensure that the introduced DNA changes are present in their sperm and ova, allowing these changes to be passed on to the next generation.
What is a practical application of transgenic mice in medical research?
Transgenic mice have been used to study hemophilia, specifically by creating transgenic sheep that express human factor IX in their milk, providing a treatment option for hemophiliacs.
Define homologous recombination in the context of creating knockout mice.
Homologous recombination is a naturally occurring process that mixes DNA from two copies of a chromosome, which is utilized in the formation of knockout mice to introduce specific mutations.
Describe the process involved in creating knockout mice.
Knockout mice are created by introducing a construct exogenously that recombines with the endogenous chromosome, aiming for the construct to replace an inactive piece of DNA with an active exon from the endogenous chromosome, thereby inactivating the endogenous DNA.
How do findings from mouse models of diseases like Huntington’s disease relate to human conditions?
Findings from mouse models do not directly apply to humans because the mice are genetically manipulated to carry human mutated genes, which may cause effects not seen in humans. The interaction between mouse and human gene forms can lead to different outcomes.
Define the limitations of using transgenic mouse models in studying human diseases.
Transgenic mouse models may not accurately reflect human conditions due to differences in gene expression, the presence of unmutated forms of genes, and the manipulation of gene copies and placements that differ from those in humans.
Do transgenic mice with Huntington’s disease also develop diabetes?
Yes, transgenic mice with Huntington’s disease were found to develop diabetes, but this does not imply that humans with Huntington’s disease will also develop diabetes.
Explain why caution is necessary when applying mouse study findings to human health.
Caution is necessary because mouse studies often involve manipulated genes and conditions that do not exist in humans, leading to potential misinterpretations of how a disease may affect human physiology.
How does the presence of the human mutated gene for Huntington’s disease in mice affect their health?
The presence of the human mutated gene for Huntington’s disease in mice can lead to various health issues, including diabetes, which may not occur in humans due to differences in gene expression and interaction.
What is the significance of the endogenous chromosome in the creation of knockout mice?
The endogenous chromosome is significant because it is the target for recombination with the introduced construct, allowing for the inactivation of specific genes in the knockout mice.
