NIH Record - National Institutes of Health

Researchers Study Enhanced Model of Down Syndrome

A young girl with Down syndrome smiling widely and holding two thumbs up
New study results may help researchers develop more precise treatments to improve learning and memory in people with Down syndrome.

Results of a new study, published in Biological Psychiatry, may help researchers develop more precise treatments to improve learning and memory in people with Down syndrome.

Researchers compared a new genetic animal model of Down syndrome to the standard model and found the updated version to be more similar to the changes seen in humans. Scientists often use different strains of mice as animal models to study human diseases because most genes in humans have similar counterparts in mice. 

NIH researchers found the new mouse model, known as Ts66Yah, had memory difficulties and behavior traits, but the symptoms were not as severe as seen with the previous mouse model. 

“A mouse model that more precisely captures the genetics of Down syndrome has important implications for human clinical trials that aim to improve cognition,” said NICHD Director Dr. Diana Bianchi, who is also a senior investigator in NHGRI’s Center for Precision Health Research and senior author of the study.

About 6,000 newborns are diagnosed with Down syndrome each year in the U.S. In most cases, these babies have a third copy of chromosome 21. An additional chromosome 21 adds an extra copy of more than 200 protein-coding genes to that person’s genome, which causes difficulties with learning, speech and motor skills.

A previous mouse model has been considered the standard for Down syndrome research, used in preclinical studies for nearly 30 years. Along with some successful cognitive treatments, such as a recent hormone-based cognitive therapy, other treatments found effective in the mouse model were not as effective in humans.

Importantly, the previous mouse model’s genome contains 45 extra genes that are irrelevant to human Down syndrome, a byproduct of how the model was developed. Humans and mice have very similar genomes, but the chromosomes that make up those genomes do not precisely align across those two species. 

To create an enhanced mouse model of Down syndrome, researchers at the University of Strasbourg, France, removed these extra 45 genes using CRISPR gene-editing technology. Bianchi’s group then compared the two mouse models and found that the extra 45 genes in the previous mouse model were affecting brain development and contributed to more severe difficulties with motor skills, communication and memory.

With this new and improved mouse model, Bianchi’s group hopes to develop more precise treatments for improving cognition with the goal of independent living skills in people with Down syndrome.

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