User:Nialldunne96/sandbox

The information already included in the "Genetically modified mouse" (Briefly explained):

A brief history of genetic modification in mice

The 2 basic methods of genetic modification in mice

A very short list of some uses and applications GM mouse research has had

Extract I am adding to the article:

Uses of transgenic mice as model organisms for research:

Mice are a useful model for genetic manipulation and research, as their tissues and organs are similar to those of humans and they carry virtually all the same genes that operate in humans.They also have advantages over other mammals, in regards to research, as they are available in hundreds of genetically homogeneous strains. Also, due to their size, they can be kept and housed in large numbers, reducing the cost of research and experiments. Genetically modified mice are particularly useful for biomedical research, in that they can be used to obtain evidence of the particular roles of genes in disease, and help uncover the fundamental molecular mechanisms involved. P.1

Originally, genetically modified mice were simply gain of function models, as geneticists were only able to add genes. However, in 1988, a paper published by Mansour and colleagues showed the feasibility of interrupting a gene in mouse embryonic stem cells. This led to the development of the technique known as gene targeting via homologous recombination, and was used to generate knockout mice. This meant genes could now be silenced with gene targeting, and both gain of function and loss of function models could be developed and limited to particular developmental stages or cell types. P.4

There are numerous landmarks in genetic manipulation technology achieved in mice including: transgenesis, gene knockout mice, systems of inducible gene expression and tissue-specific knockouts. Whereas, in other mammalian systems, the majority of these landmarks have yet to be achieved with the same efficiency. p. v  Even homeobox genes, key to development, that were discovered in drosophila melanogaster were shown to have an evolutionarily conserved function via transgenics applied to mice. P.2

Breeding strains:

In animal models used for research there is a need for genetic standardisation. This demand led to the creation of inbred mouse strains. These inbred strains are preferred for the production of transgenic mouse models due to their homogeneity. The most widely used strain for such methods is C57BL/6J (aka B6). This strain displays numerous phenotypic properties that are useful to transgenic research such as being susceptible to diet induced atherosclerosis (making theses mice useful for cardiovascular research applicable to humans). P.12

Bone marrow transplantation:

Mice can be given, permanently, a completely different hematopoietic system via transplantation of bone marrow from a different donor mouse. This donor marrow can be derived from a genetically modified mouse, making it easy to control gene function within the haematopoietic system and the subsequent cells grown and derived from that bone marrow. This includes new monocytes and tissue macrophages, which is very useful for cellular functional studies. P.281

Atherosclerosis:

Traditionally, larger animals such as rabbits were used in atherosclerosis research. However, since the 1980’s, mice began being used as models to study the development of this disease. The extensive genomic information of certain mouse strains available made them potentially useful for identifying genetic factors involved in atherosclerosis susceptibility. But only after the genetic engineering of these mice strains was the species considered a suitable model that mirrored various aspects of the human disease. P.293

The most commonly used genetically modified strain of mouse used in atherosclerosis research is ApoE-/- p.294 which has a targeted deletion that’s leads to characteristics of atherosclerosis such as development of foam cell lesions into lesions with necrotic cores and fibrous caps. This occurs in the aortic root, aorta and carotid and does not require a modified diet to be induced. P.295

Alzheimer’s:

It is impossible to attempt invasive in vivo approaches to extensively characterise the cellular and biochemical functioning of the central nervous system in humans. Therefore mice can perform the central role as a model organism to study the pathology of diseases such as Alzheimer’s. All useful transgenic mice models currently available are derived from mutated genes identified by genetic studies of families afflicted by Alzheimer’s. As experimental verification is required to prove a mutant gene is the direct cause of a given symptom or condition, and there is an absence of suitable natural models, genetic manipulation of mice is a useful tool to study such conditions. P.333

The question of whether neuritic plaques, characteristic of Alzheimer’s disease, are the cause or a symptom of the disease can be answered using transgenic mouse studies. p.337 Transgenic mice that showed all aspects of amyloid pathology found in Alzheimer’s were generated; displaying senile amyloid plaques, diffuse plaques and amyloid angiopathy. P.339 The London mutant of human APP (APP/Ld) strain of transgenic mice was created using a construct made of neuron specific elements found within the mouse thy 1 gene. P.339 From the age of one year onwards, mice of this strain develop neuritic plaques that resemble the morphology of those in Alzheimer’s sufferers. P.339-340 They also develop amyloid deposits in cerebral blood vessels, which are also characteristic of Alzheimer’s disease. P.340

Studies using the APP/Ld mice have also solved the issue of understanding how amyloid deposition changes with age and its role in the pathology of Alzheimer’s; it was shown that that amyloid deposition does increase with age, but is not caused by an increase in amyloid peptide production. Instead it is thought that this accumulation is caused by a decrease in clearance of amyloid peptides as opposed to an increase in their production. P.346