One of the K18-hACE2 that will help battle against COVID-19 (Photo by Thomas Fouchereaux, 2020).
A generous gift from Jackson Laboratory (JAX) donors will support the development of new humanized mouse models for beating COVID-19, the infectious disease caused by the novel coronavirus that has infected over 7 million worldwide, killing over 400,000 people.
JAX is fulfilling an urgent need for accurate animal models to test vaccines, neutralizing antibodies and other therapeutics against the SARS-CoV-2 virus to protect the global community against future COVID-19 pandemics. In humans, the virus enters cells by binding to ACE2, a cell surface protein that is slightly different in mice, which as a species, are not naturally susceptible to the disease. JAX is currently distributing a mouse model called K18-hACE2, donated by its creators Stanley Perlman and Paul McCray, that overcomes this obstacle through the introduction of human ACE2 genes. The resulting transgenic mouse is highly susceptible to SARS-CoV-2 infection. The dissemination of the K18-haACE2 model by JAX is a huge step forward for pre-clinical testing of vaccines and antiviral drugs.
Next-generation models for COVID-19 research
Thanks in part to recent gifts totaling $100,000 from supporters, JAX scientists will now develop innovative, more accurate mouse models for COVID-19 research that authentically mimic human responses to the viral life cycle. The new models will enable exploration of common and often lethal complications in COVID-19 patients with hypertension, diabetes or cardiovascular conditions.
Using powerful new genetic engineering technologies, scientists will precisely alter key genomic elements that have diverged evolutionarily in the mouse, allowing researchers to determine exactly how SARS-CoV-2 infects cells, how the immune system responds to the infection and how these reactions might be blocked, why COVID-19 varies so widely between patients, what drugs might prevent cases from becoming severe, and more.
The power of philanthropy
Progress Charitable Foundation DE and Tailwinds Charitable Foundation, Inc. each directed challenge grants to JAX for the development of new, precise mouse models for COVID-19. Ross Dworman, a longtime JAX supporter and former trustee of the Laboratory, and his wife Katie Dworman spearheaded this special gift effort.
“Like so many others, we wanted to take effective action to combat the pandemic,” says Dworman. “Katie and I knew that JAX would be able to provide the world’s scientific community with a critical research tool for potential vaccines and therapeutics and we’re thrilled that our grant was so quickly matched by other strong supporters.”
“This gift will help us provide the global research community with new, humanized mouse models that accurately recreate the full spectrum of human COVID-19 disease, comprising invaluable, precise new tools for SARS-CoV-2 vaccine and therapeutic development,” says Professor Nadia Rosenthal, Scientific Director for JAX Mammalian Genetics.
“The next generations of mouse models for COVID-19 research will be critical for pinpointing the genetic basis of variable clinical outcomes in this infectious disease, understanding the many facets of its pathogenesis, designing vaccines and antivirals, evaluating therapeutic approaches and testing drugs to prepare for the next wave of pathogenic attack.”