Gene knockouts are a widely used genetic engineering technique that involves the targeted removal or inactivation of a specific gene within an organism's genome. This can be done through a variety of methods, including homologous recombination, CRISPR-Cas9, and TALENs.
The Rat Genome Database (RGD) is a database of rat genomics, genetics, physiology and functional data, as well as data for comparative genomics between rat, human and mouse. RGD is responsible for attaching biological information to the rat genome via structured vocabulary, or ontology, annotations assigned to genes and quantitative trait loci (QTL), and for consolidating rat strain data and making it available to the research community. They are also developing a suite of tools for mining and analyzing genomic, physiologic and functional data for the rat, and comparative data for rat, mouse, human, and five other species.
Agouti-signaling protein is a protein that in humans is encoded by the ASIP gene. It is responsible for the distribution of melanin pigment in mammals. Agouti interacts with the melanocortin 1 receptor to determine whether the melanocyte produces phaeomelanin, or eumelanin. This interaction is responsible for making distinct light and dark bands in the hairs of animals such as the agouti, which the gene is named after. In other species such as horses, agouti signalling is responsible for determining which parts of the body will be red or black. Mice with wildtype agouti will be grey-brown, with each hair being partly yellow and partly black. Loss of function mutations in mice and other species cause black fur coloration, while mutations causing expression throughout the whole body in mice cause yellow fur and obesity.
Gene trapping is a high-throughput approach that is used to introduce insertional mutations across an organism's genome.
Mouse Genome Informatics (MGI) is a free, online database and bioinformatics resource hosted by The Jackson Laboratory, with funding by the National Human Genome Research Institute (NHGRI), the National Cancer Institute (NCI), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). MGI provides access to data on the genetics, genomics and biology of the laboratory mouse to facilitate the study of human health and disease. The database integrates multiple projects, with the two largest contributions coming from the Mouse Genome Database and Mouse Gene Expression Database (GXD). As of 2018, MGI contains data curated from over 230,000 publications.
Lethal alleles are alleles that cause the death of the organism that carries them. They are usually a result of mutations in genes that are essential for growth or development. Lethal alleles may be recessive, dominant, or conditional depending on the gene or genes involved.
Conditional gene knockout is a technique used to eliminate a specific gene in a certain tissue, such as the liver. This technique is useful to study the role of individual genes in living organisms. It differs from traditional gene knockout because it targets specific genes at specific times rather than being deleted from beginning of life. Using the conditional gene knockout technique eliminates many of the side effects from traditional gene knockout. In traditional gene knockout, embryonic death from a gene mutation can occur, and this prevents scientists from studying the gene in adults. Some tissues cannot be studied properly in isolation, so the gene must be inactive in a certain tissue while remaining active in others. With this technology, scientists are able to knockout genes at a specific stage in development and study how the knockout of a gene in one tissue affects the same gene in other tissues.
Krueppel-like factor 1 is a protein that in humans is encoded by the KLF1 gene. The gene for KLF1 is on the human chromosome 19 and on mouse chromosome 8. Krueppel-like factor 1 is a transcription factor that is necessary for the proper maturation of erythroid cells.
Transcription factor MafF is a bZip Maf transcription factor protein that in humans is encoded by the MAFF gene.
In molecular cloning and biology, a gene knock-in refers to a genetic engineering method that involves the one-for-one substitution of DNA sequence information in a genetic locus or the insertion of sequence information not found within the locus. Typically, this is done in mice since the technology for this process is more refined and there is a high degree of shared sequence complexity between mice and humans. The difference between knock-in technology and traditional transgenic techniques is that a knock-in involves a gene inserted into a specific locus, and is thus a "targeted" insertion. It is the opposite of gene knockout.
The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to create knockout mice to study. Many of the targeted alleles are designed so that they can generate both complete and conditional gene knockout mice. The IKMC was initiated on March 15, 2007, at a meeting in Brussels. By 2011, Nature reported that approximately 17,000 different genes have already been disabled by the consortium, "leaving only around 3,000 more to go".
Epistasis refers to genetic interactions in which the mutation of one gene masks the phenotypic effects of a mutation at another locus. Systematic analysis of these epistatic interactions can provide insight into the structure and function of genetic pathways. Examining the phenotypes resulting from pairs of mutations helps in understanding how the function of these genes intersects. Genetic interactions are generally classified as either Positive/Alleviating or Negative/Aggravating. Fitness epistasis is positive when a loss of function mutation of two given genes results in exceeding the fitness predicted from individual effects of deleterious mutations, and it is negative when it decreases fitness. Ryszard Korona and Lukas Jasnos showed that the epistatic effect is usually positive in Saccharomyces cerevisiae. Usually, even in case of positive interactions double mutant has smaller fitness than single mutants. The positive interactions occur often when both genes lie within the same pathway Conversely, negative interactions are characterized by an even stronger defect than would be expected in the case of two single mutations, and in the most extreme cases the double mutation is lethal. This aggravated phenotype arises when genes in compensatory pathways are both knocked out.
Europhenome is a resource for presenting, searching and analysing mouse phenotypes that were revealed by high throughput mouse phenotyping programmes such as EUMODIC.
The European Conditional Mouse Mutagenesis Program or EUCOMM is an EU-funded program to generate a library of mutant mouse embryonic stem cells for research purposes.
A knockout mouse, or knock-out mouse, is a genetically modified mouse in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function.
Reverse genetics is a method in molecular genetics that is used to help understand the function(s) of a gene by analysing the phenotypic effects caused by genetically engineering specific nucleic acid sequences within the gene. The process proceeds in the opposite direction to forward genetic screens of classical genetics. While forward genetics seeks to find the genetic basis of a phenotype or trait, reverse genetics seeks to find what phenotypes are controlled by particular genetic sequences.
The Mouse Genetics Project (MGP) is a large-scale mutant mouse production and phenotyping programme aimed at identifying new model organisms of disease.
Steve David Macleod Brown is director of the Medical Research Council (MRC) Mammalian Genetics Unit, MRC Harwell at Harwell Science and Innovation Campus, Oxfordshire, a research centre on mouse genetics. In addition, he leads the Genetics and Pathobiology of Deafness research group.
Small Maf proteins are basic region leucine zipper-type transcription factors that can bind to DNA and regulate gene regulation. There are three small Maf (sMaf) proteins, namely MafF, MafG, and MafK, in vertebrates. HUGO Gene Nomenclature Committee (HGNC)-approved gene names of MAFF, MAFG and MAFK are “v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F, G, and K”, respectively.
The agouti gene, the Agouti-signaling protein (ASIP) is responsible for variations in color in many species. Agouti works with extension to regulate the color of melanin which is produced in hairs. The agouti protein causes red to yellow pheomelanin to be produced, while the competing molecule α-MSH signals production of brown to black eumelanin. In wildtype mice, alternating cycles of agouti and α-MSH production cause agouti coloration. Each hair has bands of yellow which grew during agouti production, and black which grew during α-MSH production. Wildtype mice also have light-colored bellies. The hairs there are a creamy color the whole length because the agouti protein was produced the whole time the hairs were growing.
