Of Mice and Many Repeats: Tissue Specific Expansion in a Friedreich Ataxia Mouse Model
Publication Date
July 2019
Location
LSU Health Medical Education Building
Document Type
Abstract
Start Date
26-7-2019 9:00 AM
End Date
26-7-2019 12:00 PM
Description
Friedreich ataxia (FRDA) is a life-shortening and progressive neurodegenerative disorder with no available treatment or cure. FRDA is cause by continuous expansion of the GAA∙TTC trinucleotide repeats within the first intron of the Frataxin (FXN) gene. Early symptoms of FRDA, such as ataxia of the limbs, typically occur between the ages of five and fifteen years old, leaving most patients wheelchair bound by their late teenage years. As a direct result of this expanded repeat, FXN expression decreases and energy-hungry cells in the brain and heart are affected. Clinically, patients exhibit neurodegeneration and cardiomyopathy, with an average life expectancy of only 36.5 years. Research shows that the larger the repeats are, the more severe the disorder. Our goal is to find a way to slow down the expansion of these repeats to slow disease progression and improve patient outcomes. We have found a way to slow repeats in patient cells (primary fibroblasts) and our next step is to test our treatment in a FRDA mouse model. Research shows that repeats in the heart and brain expand in FRDA patients, therefore the purpose of our experiment is to examine the expansion rate in these same tissues in an animal model with a single human FXN (hFXN) transgene. Throughout our research, we have found that in 23 days, when the mice are first weaned, there are very few differences between the tissues within each mouse. However, after 8 weeks we begin to see differences: the brain and heart tissues show the most expansion, the ears show some expansion, and the kidneys show no expansion. Over time, repeats in these tissues continue to grow larger, as seen in mice at 6 months old. With the ability to detect changes of GAA repeats over time in our target tissues, this mouse model is a good model to test our therapy to slow progression.
Recommended Citation
Nelson, Naija S., "Of Mice and Many Repeats: Tissue Specific Expansion in a Friedreich Ataxia Mouse Model" (2019). Summer Research Internship Program. 4.
https://digitalscholar.lsuhsc.edu/srip/2019/hs/4
Of Mice and Many Repeats: Tissue Specific Expansion in a Friedreich Ataxia Mouse Model
LSU Health Medical Education Building
Friedreich ataxia (FRDA) is a life-shortening and progressive neurodegenerative disorder with no available treatment or cure. FRDA is cause by continuous expansion of the GAA∙TTC trinucleotide repeats within the first intron of the Frataxin (FXN) gene. Early symptoms of FRDA, such as ataxia of the limbs, typically occur between the ages of five and fifteen years old, leaving most patients wheelchair bound by their late teenage years. As a direct result of this expanded repeat, FXN expression decreases and energy-hungry cells in the brain and heart are affected. Clinically, patients exhibit neurodegeneration and cardiomyopathy, with an average life expectancy of only 36.5 years. Research shows that the larger the repeats are, the more severe the disorder. Our goal is to find a way to slow down the expansion of these repeats to slow disease progression and improve patient outcomes. We have found a way to slow repeats in patient cells (primary fibroblasts) and our next step is to test our treatment in a FRDA mouse model. Research shows that repeats in the heart and brain expand in FRDA patients, therefore the purpose of our experiment is to examine the expansion rate in these same tissues in an animal model with a single human FXN (hFXN) transgene. Throughout our research, we have found that in 23 days, when the mice are first weaned, there are very few differences between the tissues within each mouse. However, after 8 weeks we begin to see differences: the brain and heart tissues show the most expansion, the ears show some expansion, and the kidneys show no expansion. Over time, repeats in these tissues continue to grow larger, as seen in mice at 6 months old. With the ability to detect changes of GAA repeats over time in our target tissues, this mouse model is a good model to test our therapy to slow progression.
Comments
Mentor: Ed Grabczyk, PhD, Department of Genetics