Moffitt researchers develop more efficient approach to create mouse models

December 17, 2019

TAMPA, Fla. - Genetically engineered mouse models are often used by scientists to study how the addition, deletion or mutation of genes affects the development of disease and effects of drugs. The process of creating these genetically modified mice is extremely time consuming and expensive, which limits the ability of scientists to use their models to perform important research. Moffitt Cancer Center researchers have developed a new platform for creating genetically engineered mice to study melanoma that is significantly faster than a normal mouse model approach. Their work was published in Cancer Research.

Mouse models have enabled numerous advances in our understanding of cancer and potential treatment approaches. Scientists can add or delete genes (alleles) from particular types of cells in mice, such as melanocytes in the skin, with tissue-specific DNA-targeting approaches. Additionally, scientists often make multiple changes in different genes at the same time to determine how multiple genetic alterations affect outcomes, or they may turn genes on or off during predetermined periods of time during the mouse's life to assess how time-dependent alterations impact disease and drug treatments.

Despite the knowledge gained from mouse models, "creating mouse alleles and breeding multi-allelic melanoma-prone experimental mice is expensive, slow, and cumbersome, rendering conventional mouse modeling an inefficient method to study gene functions in vivo," explained Florian Karreth, Ph.D., assistant member of the Department of Molecular Oncology at Moffitt.

Karreth and his team wanted to develop a more efficient method of creating mice with multiple genetic modifications in melanocytes. They began by isolating embryonic stem cells from previously created genetically modified mice that had alterations in genes known to contribute to melanoma (BRAF, NRAS, PTEN and CDKN2A). Next, the researchers modified genes of these embryonic stem cells even further in laboratory cultures and injected them into embryos from the original mouse strain. These embryos were then implanted into female mice and eventually were born as chimeric mice with multiple genetic alterations.

The researchers determined that the chimeric mice were able to develop melanomas to a similar extent as mice created through the normal approach. They used their new platform to show how modulation of PTEN gene expression could affect the development and progression of melanoma, and also created melanoma cell lines from the chimera mice that could be used in laboratory experiments.

Karreth hopes that the new platform will benefit the scientific community as a whole and have allowed both the embryonic stem cells lines and the melanoma cell lines to be available to the entire melanoma research community. "Given that it takes less than 2.5 months from embryonic stem cell targeting to inducing melanomagenesis in experimental chimeras, we anticipate that our platform has the potential to dramatically accelerate melanoma studies in mice," he said.
-end-
This study was supported by grants from the National Institutes of Health, Melanoma Research Alliance, American Cancer Society, Moffitt Cancer Center Skin SPORE Career Development Program, Miles for Moffitt and a Harry J. Lloyd Charitable Trust Career Development Program.

About Moffitt Cancer Center

Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 51 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt's scientific excellence, multidisciplinary research, and robust training and education. Moffitt is a Top 10 cancer hospital and has been nationally ranked by U.S. News & World Report since 1999. Moffitt's expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 6,500 team members, Moffitt has an economic impact in the state of $2.4 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, Twitter, Instagram and YouTube.

H. Lee Moffitt Cancer Center & Research Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.