Gonzalo López SánchezSEGUIRMadrid Updated: Save Send news by mail electrónicoTu name *
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In January of this year the scientists of the Laboratories of the Jackson (JAX), in Bar Harbour, Maine (Usa), received an avalanche of orders of laboratory mice . The epidemic was skyrocketing in China and in anticipation of what was to come, hundreds of researchers around the world began calling for animals to be able to investigate their vaccine candidates against SARS-CoV-2.
The scientists demanded copies of a transgenic mouse “humanized”, by the name of K18-hACE2. Its main feature is that their cells expressing the ACE2 receptor, human coronaviruses used to infect the cells, and not the mice, that the coronavirus doesn’t recognize it. The problem is that in January the mice K18-hACE2 not were alive anywhere in the world : one of them only stayed for a little bit of sperm stored in the freezers of the Laboratories of the Jackson.
“ The mice have been a bottle-neck for research , ” he explained to ABC Javier Ortego , a researcher at the Center for Animal Health Research (CISA), in Madrid. “Earlier this year, described that this was the appropriate animal model. All the world wanted them, but for as much as you can speed up the process of breeding takes time, it is like making a tree grow”.
Javier Ortego, who will work with these mice and other animals in the process of testing of two vaccine candidates developed in Spain, has explained that maintaining colonies of mice, is expensive, and it is therefore more usual is to freeze them and revive them when they are needed. But doing so takes time: as you have indicated to this researcher, the gestation in mice lasts about 20 days, and your sexual maturity does not arrive until after two months .
that’s why, and despite all the efforts of the company, JAX will not begin to distribute these animals to large-scale until the end of June, thus marking the times in the development of dozens of vaccine candidates, including several spaniards. Will have more than 250 orders of researchers from all over the world and distribute small groups of animals in special boxes.
A “Noah’s Ark” of laboratory mice
The Laboratories Jackson (JAX) are from decades ago as a seed bank, whose purpose is to preserve genetic diversity for future generations, but to apply these principles to laboratory mice. Today, count with 11.000 strains preserved in tanks of liquid nitrogen at -196ºC , ready to be recovered and injected in mice by means of assisted reproduction techniques. Each year they sold three million mice to more than 20,000 researchers around the world, at a price that only intend to cover the expenses, since they are a non-profit organization, under the auspices of the National Institutes of Health (NIH), united States.
The pandemic coronavirus “forced them to accelerate from zero to a hundred,” in a few weeks, as has been explained to ABC Cat Lutz, senior director of the repository of the Laboratories Jackson, in charge of the breeding process and care of these animals. As has been said, on the basis of a handful of vials of sperm of mouse, at the beginning of this year the team of JAX began a process of in vitro fertilization (IVF), large-scale, designed to generate a new colony of mice hACE2 that could be increased in size to meet the world’s needs.
Lower your shoulders fell a very important responsibility because JAX is the only provider of these animals : “JAX is not the sole repository of mice ACE2”, he explained, the Cat Lutz. “However, the other deposits and commercial vendors have variations of this model that does not tend to be useful in experiments of infectivity,” he clarified. But “JAX is the only repository that has the model of the laboratory of Stanley Perlman, used to investigate the SARS in 2003 and that it has been predicted that it is useful to study vaccines and treatments for the COVID-19”.
The origin of the transgenic mice
Stanley Perlman is a researcher at the University of Iowa (USA) in 2007 developed the mice (K18-hACE2 next to Paul McCray . His work began with the epidemic of SARS-CoV-1, which occurred between the years 2002 and 2003, and that triggered the research of vaccines and the biology of a coronavirus very similar to SARS-CoV-2.
Cat Lutz, senior director of repository of animal Laboratories Jackson – The Jackson Laboratory
This year it was confirmed that, like the coronavirus, 2002 and 2003, the SARS-CoV-2 enters the human cells through the receptor ACE2, so that it became evident that the mouse K18-hACE2 is the model suitable to study the infection and, therefore, the possible protection of any vaccine. Unlike a normal mouse, this animal embodies a human gene that makes their cells to express the receptor that is of interest to scientists.
why do they lack for the vaccine?
In these moments the race for the vaccine against the coronavirus is led by ten projects, according to the World Health Organization (WHO). Have the backing of large institutions and companies of China, the united States and the United Kingdom, and are already in clinical phase, that is to say, by evidence of efficacy and safety in humans . In several cases, at the same time they are doing tests on monkeys and other laboratory animals.
But the bulk of the vaccine candidates are not yet in clinical trials, but in preclinical phase. There are 110 projects in development, which in many cases still have to go through tests with small laboratory animals before proceeding to trials more expensive and complex, with animals of higher size or in healthy volunteers. This is the case, for example, of two vaccine candidates developed at the National Center of Biotechnology (CNB-CSIC) led by Luis Enjuanes Mariano Esteban. And that is where the transgenic mice K18-hACE2 have a vital role, since they are the first point where we can study if a vaccine gives protection or not.
Mouse albino BALB/c, widely used in all kinds of experiments – The Jackson LaboratoryTrabajar without the transgenic mice
as has been explained to Javier Ortega, in the absence of mice K18-hACE2 there are workarounds, such as working with hamsters , which may mimic a mild infection. In addition, as explained, before moving on to the mice trasngénicos and the tests with live viruses, which are made in facilities of high-level biosafety (BSL-3), the first tests are done in laboratory mice, “normal”, as the strains C57BL/6 and BALB/c. These are the ones that are doing time in the laboratory of Mariano Esteban, in the CNB.
With these animals you can’t study the protection conferred by a vaccine, because they are not susceptible to the disease, but yes you can evaluate other things, such as if a candidate triggers the production of antibodies, or what dose, or route of administration are the most convenient.
as he explained during an interview, Luis Enjuanes, in his laboratory on a principle not only made an order of transgenic mice K18-hACE2, but also commissioned the department of transgenesis of the CNB to prepare their own transgenic mice. Finally, the researcher Sagrario Ortega, head of the Unit of genome Editing in Mouse at the Spanish National Cancer Research Centre (CNIO) has also initiated two-way generation of mice susceptible to the virus.
“Initially, going to have a little delay –in the development of its candidate vaccine– but we believe that at the end of summer, we will have limited amounts of transgenic mice ,” said Enjuanes.
These special mice are another proof of how important it is to have the facilities and scientists of high level to be able to respond to crisis as complex as the triggered by the COVID-19.