question: If results from mouse models are not applicable to humans most of the time, why are they still used today?
comment: Mice (along with many other mammals) have a lot of similarities with humans, so testing on them can be a good starting point before you subject humans to testing, where there could be more ethical issues if something goes wrong. Mice also have the advantages of being cheap to acquire and quick to mature and have offspring. Additionally, mice can be bred or genetically modified to better fit researchers' needs.
passages: An article in "The Scientist" notes, "The difficulties associated with using animal models for human disease result from the metabolic, anatomic, and cellular differences between humans and other creatures, but the problems go even deeper than that" including issues with the design and execution of the tests themselves.
   Section::::Limitations.
  
  While mice are by far the most widely used animals in biomedical research, recent studies have highlighted their limitations. For example, the utility of rodents in testing for sepsis, burns, inflammation, stroke, ALS, Alzheimer's disease, diabetes, cancer, multiple sclerosis, Parkinson's disease, and other illnesses has been called into question by a number of researchers. Regarding experiments on mice, some researchers have complained that "years and billions of dollars have been wasted following false leads" as a result of a preoccupation with the use of these animals in studies.
   For example, researchers have found that many mice in laboratories are obese from excess food and minimal exercise which alters their physiology and drug metabolism. Many laboratory animals, including mice, are chronically stressed which can also negatively affect research outcomes and the ability to accurately extrapolate findings to humans. Researchers have also noted that many studies involving mice are poorly designed, leading to questionable findings.
   Controversy occurred in the scientific community over the use of mouse models in research into sepsis in 2013, when scientists published a review of the mouse immune system compared to the human immune system, and showed that on a systems level, the two worked very differently; the authors noted that as of the date of their article over 150 clinical trials of sepsis had been conducted in humans, almost all of them supported by promising data in mice, and that all of them had failed. The authors called for abandoning the use of mouse models in sepsis research; others rejected that but called for more caution in interpreting the results of mouse studies, and more careful design of preclinical studies. One approach is to rely more on studying biopsies and clinical data from people who have had sepsis, to try to identify biomarkers and drug targets for intervention and prognosis..
   This is a particularly crucial item of consideration in spectrum disorders such as autism. Autism is a disorder whose symptoms can be divided into two categories: (i) deficits of social interactions and (ii) repetitive behaviours and restricted interests. Since mice tend to be more social creatures amongst all members of the order "Rodentia" currently being used as model organisms, mice are generally used to model human psychiatric disorders as closely as possible. Particularly for autism, the following work-arounds are currently in place to emulate human behavioural symptoms:
   While mice, rats and other rodents are by far the most widely used animals in biomedical research, recent studies have highlighted their limitations. For example, the utility of the use of rodents in testing for sepsis, burns, inflammation, stroke, ALS, Alzheimer’s, diabetes, cancer, multiple sclerosis, Parkinson’s disease and other illnesses has been called into question by a number of researchers. Regarding experiments on mice in particular, some researchers have complained that “years and billions of dollars have been wasted following false leads” as a result of a preoccupation with the use of these animals in studies. 
   Techniques for genetic manipulation are available in the mouse, which is commonly used to model human disease. Although published knockouts exist for approximately 60% of mouse genes, a large majority of common human diseases do not have a knockout mouse model. Knockout rat models are an alternative to mice that may enable the creation of new gene disruptions that are unavailable in the mouse. Knockout rat models can also complement existing transgenic mouse models. Comparing mouse and rat mutants can facilitate the distinction between rodent-specific and general mammalian phenotypes.
  
  Section::::Production challenges.
   As of 2018, there are about 20 "TARDBP" mouse models, a dozen "FUS" mouse models, and a number of "C9orf72", "PFN1", and "UBQLN2" mouse models. There are also new methods of developing animal models, including viral transgenesis, in which viruses are used to deliver mutant genes to an animal model, and CRISPR/Cas9, which can be used to give an animal model multiple mutated genes. Both of these methods are faster and cheaper than traditional methods of genetically engineering mice; they also allow scientists to study the effects of a mutation in mice of different genetic backgrounds, which better represents the genetic diversity seen in humans.
   Section::::Replacing animal testing.
  
  In the early phase of drug development, animal models were the only way of obtaining in vivo data that would predict the human pharmacokinetic responses. However, experiments on animals are lengthy, expensive and controversial. For example, animal models are often subjected to mechanical or chemical techniques that simulate human injuries. There are also concerns with regards to the validity of such animal models, due to deficiency in cross-species extrapolation. Moreover, animal models offer very limited control of individual variables and it can be cumbersome to harvest specific information.
   Mice are the most commonly used vertebrate species, popular because of their availability, size, low cost, ease of handling, and fast reproduction rate. Mice are quick to reach sexual maturity, as well as quick to gestate, where labs can have a new generation every three weeks as well as a relatively short lifespan of two years.
  
  They are widely considered to be the prime model of inherited human disease and share 99% of their genes with humans. With the advent of genetic engineering technology, genetically modified mice can be generated to order and can cost hundreds of dollars each.
   Mice are common experimental animals in laboratory research of biology and psychology fields primarily because they are mammals, and also because they share a high degree of homology with humans. They are the most commonly used mammalian model organism, more common than rats. The mouse genome has been sequenced, and virtually all mouse genes have human homologs. The mouse has approximately 2.7 billion base pairs and 20 pairs of chromosomes.
   Animals such as the fruit fly "Drosophila melanogaster", the zebrafish, the chicken and the house mouse, serve a major role in science as experimental models, both in fundamental biological research, such as in genetics, and in the development of new medicines, which must be tested exhaustively to demonstrate their safety. Millions of mammals, especially mice and rats, are used in experiments each year.
  
  A knockout mouse is a genetically modified mouse with an inactivated gene, replaced or disrupted with an artificial piece of DNA. They enable the study of sequenced genes whose functions are unknown.
  
  Section::::Practical uses.:In medicine.
   Rat models have been used to advance many areas of medical research, including cardiovascular disease, psychiatric disorders (studies of behavioral intervention and addiction), neural regeneration, diabetes, transplantation, autoimmune disorders (rheumatoid arthritis), cancer, and wound & bone healing. While the completion of the rat genome sequence provides very key information, how these diseases relate to gene function requires an efficient method to create knockout rat models in which specific genomic sequences are manipulated.
   According to the U.S. Department of Agriculture (USDA), the total number of animals used in that country in 2005 was almost 1.2 million, excluding rats and mice. Some animal rights supporters believe that alternatives exist for animal models in research; however the vast majority of scientists believe there are no adequate alternatives which truly replace the roles which research animals play. In fact, recent research shows that 98% of the current drug pipeline relies on either dogs or non-human primates.
   Humanized mouse
  
  A humanized mouse is a mouse carrying functioning human genes, cells, tissues, and/or organs. Humanized mice are commonly used as small animal models in biological and medical research for human therapeutics. Immunodeficient mice are often used as recipients for human cells or tissues, because they can relatively easily accept heterologous cells due to lack of host immunity. Traditionally, the nude mouse and severe combined immunodeficiency (SCID) mouse have been used for this purpose, but recently the NCG mouse, NOG mouse and the NSG mouse have been shown to engraft human cells and tissues more efficiently than other models.
   The US National Institute on Aging currently funds an intervention testing programme, whereby investigators nominate compounds (based on specific molecular ageing theories) to have evaluated with respect to their effects on lifespan and age-related biomarkers in outbred mice. Previous age-related testing in mammals has proved largely irreproducible, because of small numbers of animals and lax mouse husbandry conditions. The intervention testing programme aims to address this by conducting parallel experiments at three internationally recognised mouse ageing-centres, the Barshop Institute at UTHSCSA, the University of Michigan at Ann Arbor and the Jackson Laboratory.
   Some studies suggests that inadequate published data in animal testing may result in irreproducible research, with missing details about how experiments are done are omitted from published papers or differences in testing that may introduce bias. Examples of hidden bias include a 2014 study from McGill University which suggests that mice handled by men rather than women showed higher stress levels. Another study in 2016 suggested that gut microbiomes in mice may have an impact upon scientific research.
  
  Section::::Market size.
   Ethical concerns, as well as the cost, maintenance and relative inefficiency of animal research has encouraged development of alternative methods for the study of disease. Cell culture, or "in vitro" studies, provide an alternative that preserves the physiology of the living cell, but does not require the sacrifice of an animal for mechanistic studies. Human, inducible pluripotent stem cells can also elucidate new mechanisms for understanding cancer and cell regeneration. Imaging studies (such as MRI or PET scans) enable non-invasive study of human subjects. Recent advances in genetics and genomics can identify disease-associated genes, which can be targeted for therapies. 
   BULLET::::- Wellcome Trust description of model organisms
  
  BULLET::::- National Institutes of Health Comparative Medicine Program Vertebrate Models
  
  BULLET::::- NIH Using Model Organisms to Study Human Disease
  
  BULLET::::- National Institutes of Health Model Organism Sharing Policy
  
  BULLET::::- Why are Animals Used in NIH Research
  
  BULLET::::- The Future of Cell Biology: Emerging Model Organisms
  
  BULLET::::- Disease Animal Models – BSRC Alexander Fleming
  
  BULLET::::- Emice – National Cancer Institute
  
  BULLET::::- Reproducibility: Use mouse biobanks or lose them
  
  BULLET::::- Knock Out Mouse Project – KOMP
  
  BULLET::::- Mouse Biology Program
  
  BULLET::::- [https://www.mmrrc.org/ Mutant Mouse Resource & Research Centers [National Institutes of Health, supported Mouse Repository]]
   There are technologies that completely avoid the use of mice or other non-human mammals in the process of discovering antibodies for human therapy. Examples of such systems include various "display" methods (primarily phage display) as well as methods that exploit the elevated B-cell levels that occur during a human immune response.
  
  Section::::Antibodies for human therapy derived without using mice.:Display methods.
   Section::::Research use.
  
  Mice, rats, and humans share all but approximately 1% of each other's genes making rodents good model organisms for studying human gene function. Both mice and rats are relatively small, easily handled, have a short generation time, and are genetically inbred. While mice have proven to be a useful rodent model and techniques have been developed for routine disruption of their genes, in many circumstances rats are considered a superior laboratory animal for studying and modeling human disease. 
   Immune compromised mice have become of particular interest for studying the Human Immunodeficiency Virus (HIV), how it interacts with the host in human lymphoid organs, as well as how treatments work "in vivo". While HIV normally cannot infect mice, SCID mice have been used to study HIV. Prior to the use of humanized SCID mice, ape models were used to study HIV due to their genetic similarity to humans. However, due to the endangered status of chimps, the cost of maintaining them, and the slight differences between human and chimp interactions with HIV, humanized mice have been accepted as a more effective model organism for the study of this disease.
   Medical device studies also use this basic premise. Most studies are performed in larger species such as dogs, pigs and sheep which allow for testing in a similar sized model as that of a human. In addition, some species are used for similarity in specific organs or organ system physiology (swine for dermatological and coronary stent studies; goats for mammary implant studies; dogs for gastric and cancer studies; etc.).
   Mice are currently the laboratory animal species most closely related to the humans for which the knockout technique can easily be applied. They are widely used in knockout experiments, especially those investigating genetic questions that relate to human physiology. Gene knockout in rats is much harder and has only been possible since 2003.
   SCID mice have allowed for increased research on a wide range of topics, including the development and pluripotency of human HSC, human-specific diseases and their interactions with the human immune system, vaccination, and cancer. SCID mice with human immune cells are able to respond to pathogens such as viruses and create antibodies against them, which has helped scientists better understand how the human immune system protects against pathogen infection. For example, they have been used to study Dengue virus and malaria, as well as to assess the efficacy of drugs that target these diseases.
  