How accurate are the rat studies?

Mice and humans have an 80% identical genome, making mice a suitable substitute and beneficial for humans in medical research. A recent article by two University of Michigan biologists Ben-Yang Liao and Jianzhi Zhang mentioned how some of the same genes can work differently in mice and humans - and how one The number of essential genes for humans is completely absent in mice.

'It has been suggested that the lack of the same gene in mice and humans produces the same phenotype (an observable trait such as having or not having a specific disease). It is the foundation of using mice to study human diseases. Our results show that that may not always be true. ' ecological assistant professor of evolution and biology Zhang said.

Associate Professor Zhang and his graduate student focused on studying so-called essential genes - genes, through which their effects on survival or fertility, are needed. for organisms to reach sexual maturity and reproduction. They then targeted 120 essential human genes whose mice had the same copy for these genes that were also studied. Next, they refer to the database of experimental results in which mouse genes are equivalent to humans being lost or 'damaged'.

If those 120 essential human genes are also essential in mice, losing any of them can cause infertility or death before the reproductive age. But the database showed an unexpected deviation.

Picture 1 of How accurate are the rat studies?

Experimental mice.(Photo: wikipedia)


'We were surprised, 22% of the 120 essential human genes are not essential in mice ,' said Zhang. 'I think there are only a few, but I didn't expect this rate to be too high.'

Curiously, the researchers wanted to understand why the 'necessity' of some genes changed in time since humans and mice shared the most recent common ancestor. A closer look at the protein products of individual genes that are essential in mice, but they found that, a much higher percentage than expected in the vacuole, functions as a but landfill is an extremely important landfill.

The main function of vacuole is to contain and decompose waste and cytotoxic substances. In humans, without the vacuole proteins, these wastes and toxins build up, often leading to deadly neurological diseases.

The same thing happened in mice, but at a much later stage, often through reproductive ages. As a result, 'many proteins in these vacuole proteins are not so essential to mice. Even without these proteins, mice can survive to reproduce. '

Researchers speculate that in the course of primate evolution, life expectancy increases and reproductive age is delayed, effective waste management is becoming increasingly important.

Their additional analysis results demonstrate this thought. By developing an integrated portfolio of metabolic rate and reproductive age, and then using that category to compare people and mice, researchers determined that the amount of waste produced above 1 The body weight from birth to reproductive age is about 18 times higher in humans than in mice.

'Therefore, waste management is much more important in humans than in mice to maintain proper cell function until the time of reproduction. And when a biological process becomes more important for a species, the genes involved in that process tend to become essential. '

Associate Professor Zhang acknowledged that this study contained only a small number of genes, and he hoped that other researchers would be able to confirm these results as more and more information about human and mouse genes is available. .

'If our research is not biased, these results will have some important implications. First of all, in many genome projects, people deduced gene function by using information from other model organisms. We need to be careful when doing this because we now know that a majority of genes can have different functions or different importance in different species. ' Associate Professor Zhang said.

In addition, the results raise concerns about the widespread use of mouse models to study human disease.

According to Associate Professor 'Our research does not think mouse models are useless. Even for genes that change that essential, mouse models can still provide useful information. For example, it can tell us about the molecular function of genes, even if the importance of genes varies among species. But for some diseases, such as neuropathy involving vacuole proteins, the phenotype is so different that it may be necessary to establish a model of primates. '