The mouse transporter is not located on the mitochondria, so FIAU cannot enter the mitochondria and exert its toxic effect. Clearly, mice are not the perfect model of every human disease, but scientists still use them to study most ailments out of convenience.
The mouse is the most commonly used model organism in human disease research (Rosenthal and Brown, 2007). Mouse models have been used extensively to provide insight into the mechanisms underlying many diseases, to explore the efficacy of candidate drugs and to predict patient responses.
Without the receptor, serotonin cannot transmit signals to nearby cells. If drugs are made to target receptors that are only present in mice, they will not work in humans. As a result, treatments for depression, schizophrenia, anxiety, Alzheimer’s, and other disorders may be very helpful in mice but would fail to treat the diseases in humans.
The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research.
The mice used in these studies are termed PDX mice and are often called human avatars. To produce these avatars, extracts from human cancers (obtained by biopsies or surgical excisions) are injected into mice, thereby creating mice purportedly expressing the injected cancer.
It has been thought that such "precision oncology" models will remedy the problems with cell-line-derived cancer tissue, and will identify tumor markers, genetic targets, and effective treatments for a patient's specific cancer.
Researchers characteristically address the very high attrition rate for drugs developed from animal research by postulating that “better” techniques with animals are needed. Various approaches to improve the predictability of these stand-ins for human cancers have been tried without success.
In general, cancer animal research (see here, here, and here) has a failure rate of at least 95 percent, as determined by the results of clinical trials based partly on mouse studies. The few "successes" are usually clinically irrelevant, providing minimal or no real-life value.
Mice Are Telling Cancer Researchers: Give It Up. It is widely known that mouse research to study human cancers is fraught with unreliability. Scientists have for decades attempted to replicate human cancer growth and treatment responses in mice by disabling their immune systems and grafting human-cell-line-based cancers onto them, ...
Despite decades of research model manipulation, mice are no better at recapitulating the course or treatment responses of human cancers. Second, the logical transition to human-relevant cancer research methods is overdue.
A recent study published in Nature by Hodge et al. showed that even though humans and mice share the same genes , they function differently in the cells of different animals. In order for a cell to perform its job properly, it needs to make specific proteins unique to that cell. These proteins are the worker bees, the ones that actually do the job of a cell, and the directions used to make these proteins are encoded in sections of DNA called genes. A gene is like a very important sentence of a book that a cell can read every time it wants to make the protein encoded by the gene. The more the cell reads the gene, the more the gene is expressed, and the more protein that is made. All of the 20,000 genes in the human genome can be read an infinite number of times, allowing a cell to make many different types of proteins particular to its needs.
FIAU was toxic in humans because of a specific protein located on our mitochondria, the structures that generate energy in our cells. This protein transports the drug from empty space in the cell into the mitochondria. Once the drug is let in, it poisons the mitochondria.
Serotonin, a chemical that regulates mood, sends messages between neurons by binding to its receptor on the receiving neuron’s surface.
These proteins are the worker bees, the ones that actually do the job of a cell, and the directions used to make these proteins are encoded in sections of DNA called genes . A gene is like a very important sentence of a book that a cell can read every time it wants to make the protein encoded by the gene.
Consequently, a drug designed to act on the serotonin receptor will affect the left neuron on the left but not the one on the right. To compare genes in humans and mice, Hodge et al. used a technique called DNA sequencing to identify the DNA that makes up all the genes in human and mouse brain cells.
Just like a dog cannot eat chocolate because their liver cannot break down the caffeine, humans have also died because their bodies cannot absorb or process the drugs originally tested in mice.
In humans, the transporter protein is also located on the mitochondrial membrane, so FIAU enters the mitochondria and poisons this important energy-generating part of the cell. The mouse transporter is not located on the mitochondria, so FIAU cannot enter the mitochondria and exert its toxic effect.