Project Summary

“We discovered that genetic variability heavily influences bone and muscle mass in a manner not observable with standard inbred mice”

Bone and muscle mass can be impacted by a variety of positive and negative stimuli. Our lab focuses specifically on mechanical unloading and the response of the musculoskeletal system to non-ambulatory states. Studies from our lab and others have previously reported a potential influence of genetics in this process, and we were interested in diving more deeply into this topic.

Through the DO Pilot Grant, we discovered that genetic variability heavily influences bone and muscle mass in a manner not observable with standard inbred mice. These results support the hypothesis that certain musculoskeletal responses are heritable, and indicates that an individual’s genetic background can contribute to the catabolic effects of unloading.

Natural genetic variation in the CD8+ T cell response to microbial exposure

PRINCIPAL INVESTIGATORS
Norah L. Smith
PhD / Senior Research Associate

INSTITUTION
Cornell University

Project Summary

“Using J:DO mice in conjunction with our existing experimental models will facilitate a more complete understanding of CD8+ T cell function.”

CD8+ T cells are a critical component of the adaptive immune system. In response to infection or cancer, activated CD8+ T cells adopt a multitude of fates. The diversity of T cells generated play a significant role in disease prognosis and recovery. Our lab seeks to understand the developmental, environmental and genetic factors that contribute to functional cellular diversity within the CD8+ T cell pool.

Up to 40% of variation in the human immune system can be explained by genetic factors. Conventional inbred models make it difficult to assess how genetics contribute to T cell function. J:DO mice are a useful model for systematic evaluation of the genetic factors regulating immune cell behavior.

Modeling Variability in Cognitive Responses to Recombinant GDF11 Treatment Using Aged Diversity Outbred Mice

PRINCIPAL INVESTIGATORS
Robert Pazdro
Associate Professor

INSTITUTION
University of Georgia

Project Summary

“Humans are a far more genetically diverse population than inbred mice, and by incorporating this diversity into our experiments, we hope to expand our understanding of neurological responses to treatment”

Over the past several years, preclinical studies have shown that levels of circulating GDF11 decline during aging and that supplemental GDF11 treatment increases brain angiogenesis and neurogenesis, reduces inflammation and senescence, and can restore cognitive function in rodent models of neurological disease. While these discoveries have sparked excitement for the clinical potential of GDF11, a major blind spot is obvious: to this point, studies have only been performed in standard rodent strains containing little or no genetic variation.

Our goal with the DO Pilot Grant is to determine the impact of genetic variation on GDF11 responses to pave the way for broader translational, and eventually, clinical studies of GDF11. Humans are a far more genetically diverse population than inbred mice, and by incorporating this diversity into our experiments, we hope to expand our understanding of neurological responses to treatment.

Characterization of the cardiac electrophysiology and calcium dynamics in diversity outbred (DO) mice

PRINCIPAL INVESTIGATORS
Eleonora Savio-Galimberti
Associate Professor

INSTITUTION
Lankenau Institute for Medical Research

Project Summary

“The presence of genetic variability in DO mice makes them an ideal bridge between standard mouse models and human research”

One of the most common practices in biomedical research is the use of inbred mice. While initially convenient to decrease the potential variability in specific outcomes measured, the lack of genetic diversity in inbred mice limits their representativity as a translational, cross-species animal model. This is particularly true in cardiovascular research where known genetic variants are key contributors to disease.

Our laboratory is using the DO Pilot Grant to better understand the impact of genetic diversity on cardiac physiology and disease-like arrhythmias. The presence of genetic variability in DO mice makes them an ideal bridge between standard mouse models and human research. By conducting in-vivo and ex-vivo studies, we aim to validate these mice as a key translational model in cardiovascular research, and discover novel pathways with the potential to influence cardiac dysfunction.

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