#mouse model

Targeting Zombie Cells

Senescent cells are those that have stopped multiplying but not yet died. Sometimes referred to as ‘zombie cells’, they accumulate with age and can release chemicals that can cause cancer. To better understand how senescent cells might be involved in the initiation and development of lung tumours, researchers have a developed a mouse model allowing examination of senescent cells within the tumour microenvironment. The team discovered that senescent macrophages – a type of white blood cell of the immune system – release pro-tumour factors creating an environment that fosters lung tumour growth. However, when the researchers treated mice with lung tumours with a drug that specifically destroys these ‘zombie’ macrophages, the size of the tumours (highlighted in green in these lung sections) reduced dramatically (right) compared to those without treatment (left). Excitingly, this shows that targeting senescent macrophages could be an effective new way to treat or even prevent these tumours.

Written by Sophie Arthur

Image from work by Scott Haston and colleagues

Developmental Biology and Cancer Programme, Birth Defects Research Centre, UCL Institute of Child Health, London & Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Cancer Cell, June 2023

Intravenous Injection of Coronavirus Disease 2019 (COVID-19) mRNA Vaccine Can Induce Acute Myopericarditis in Mouse Model

Abstract

Background

Post-vaccination myopericarditis is reported after immunization with coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. The effect of accidental intravenous injection of this vaccine on the heart is unknown.

Methods

We compared the clinical manifestations, histopathological changes, tissue mRNA expression, and serum levels of cytokine/chemokine in Balb/c mice at different time points after intravenous (IV) or intramuscular (IM) vaccine injection with normal saline (NS) control.

Results

Although significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1–2 days post-injection (dpi), only IV group developed histopathological changes of myopericarditis as evidenced by cardiomyocyte degeneration, apoptosis, and necrosis with adjacent inflammatory cell infiltration and calcific deposits on visceral pericardium, although evidence of coronary artery or other cardiac pathologies was absent. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen expression by immunostaining was occasionally found in infiltrating immune cells of the heart or injection site, in cardiomyocytes and intracardiac vascular endothelial cells, but not skeletal myocytes. The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose. Cardiac tissue mRNA expression of interleukin (IL)-1β, interferon (IFN)-β, IL-6, and tumor necrosis factor (TNF)-α increased significantly from 1 dpi to 2 dpi in the IV group but not the IM group, compatible with presence of myopericarditis in the IV group. Ballooning degeneration of hepatocytes was consistently found in the IV group. All other organs appeared normal.

Conclusions

Gene Team

As an organism evolves, its DNA does too. Tracing the history of how it mutates, moves and duplicates can reveal surprises, like similar genes – paralogues – in distant corners of the genome. Here researchers use optical projection tomography to follow the activity of a gene called Utrn (highlighted in red) in a mouse embryo. Combining patterns of bioluminescence and fluorescence to reconstruct this 3D image reveals Utrn in many of the mouse’s early tissues. Utrn has a paralogue, Dmd, another important developmental gene found to be faulty in Duchenne muscular dystrophy in mice and humans. While these similar genes are expressed differently in health and disease, researchers believe it might be possible for Utrn to 'compensate' for Dmd in some patients. This mouse model will aid the next challenge – testing drugs to coax these related genes into working together.

Read more about this research from the Epigenetic Memory Group at the MRC London Institute of Medical Sciences here

Written by John Ankers

Video from work by Hannah J. Gleneadie and Beatriz Fernandez-Ruiz, and colleagues

Epigenetic Memory Group, MRC London Institute of Medical Sciences (LMS), Imperial College London, Du Cane Road, London, UK

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Communications Biology, March 2023

Disrupted Journey

It can be hard to adapt when you move to a new place. Luckily, the same is true for cancer cells trying to migrate from one organ to another – a process called metastasis. Most bowel cancer cells that try to set up a second home in the liver die in the process, but a few particularly hardy ones can manage it, and create a dangerous secondary tumour. To study this, and learn how to prevent it, researchers introduced human tumour cells into a mouse liver (pictured). They discovered that cells capable of spreading had particularly high levels of a protein, PCK1, which helps build nucleotides – components of DNA. When the tumours were treated with a drug that blocks nucleotide formation, usually used for arthritis patients, they were no longer able to metastasise, raising hopes that it, and other similar drugs, might help stop bowel cancer in its tracks.

Written by Anthony Lewis

Image from work by Norihiro Yamaguchi, Ethan M Weinberg and Alexander Nguyen, and colleagues

Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, December 2019

How Zika Harms

Zika virus has been on a world tour since its discovery in Uganda in 1947. Spread by mosquito bites, it travelled from Africa up through Asia, eventually reaching the Americas. Along the way it has evolved into two distinct lineages – African and Asian/American. Although it only causes mild symptoms in healthy adults, Zika infection in pregnancy can be devastating, leading to miscarriage and problems with brain development (microcephaly). Curiously, this seems to be a relatively recent effect, leading researchers to wonder whether the virus picked it up along its travels. To find out, they exposed pregnant mice to different versions of Zika from around the world and looked at the effects on their foetuses, around three quarters of the way through development. All three types caused serious problems (second, third and fourth panels) compared with an uninfected mother (first panel), proving that Zika’s harmful properties in pregnancy are nothing new.

Written by Kat Arney

Image from work by Anna S. Jaeger and colleagues

Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities; St. Paul, MN, USA

Image originally published under a Creative Commons Licence (BY 4.0)

Published in PLOS Neglected Tropical Diseases, April 2019

Crossed Wires

These colourful structures are human nerve cells, growing and connecting inside a brain. But it’s not a human brain – this a mouse brain, into which human nerve cells have been transplanted. Studying nerve connections inside a living human brain is extremely difficult, but animal models don’t accurately reflect the complexity and molecular makeup of human cells. Researchers have now developed a clever technique to solve the problem: human skin cells are reprogrammed into stem cells, then converted into nerve cells that will grow inside a mouse’s skull. Comparing nerve cells grown from people with the developmental disorder Down syndrome with those from unaffected individuals is providing important new insights into what happens in a healthy brain as it grows and develops and what might be going wrong in Down syndrome. Hopefully, the discoveries from this ingenious approach will lead to future treatments to improve life for people with the condition.

Read more about this research from the MRC LMS

Written by Kat Arney

Image from work by Raquel Real, Manuel Peter and Antonio Trabalza, and colleagues

MRC London Institute of Medical Sciences, London, UK

Image copyright held by the original authors

Research published in Science, October 2018

rat/mouse model by https://www.lauramathewsart.com/