Undergraduate Honors Thesis


The role of Ubqln2 in ALS mouse models and cortical neuron stress response Public Deposited

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  • Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease that affects the upper and lower motor neurons of the nervous system. ALS cases are often associated with frontotemporal dementia (FTD). While 90% of cases are sporadic, 10% of cases are genetic and known as familial amyotrophic lateral sclerosis (fALS). One mutated gene that leads to fALS is Ubiquilin2 (Ubqln2), which plays a role in the ubiquitin proteasome system by acting as a shuttling factor. However, the precise function of UBQLN2 and how it leads to ALS is not entirely understood. Previous studies show that when UBQLN2 is lost, there is an abundance of the domesticated retrotransposon, PEG10. Our goal is to explore how the loss of Ubqln2 affects in-vivo mouse models and how UBQLN2 and PEG10 are interacting in cortical mouse neurons upon cellular stress. Using Ubqln2-/- mouse models that develop neurodegenerative disease, we can determine at what age neuromotor defects begin to show through a series of monthly neuromotor tests. Using cortices isolated from WT or Ubqln2-/- embryos harvested from Ubqln2 breeding pairs, we can induce stress granule formation to investigate where UBQLN2 and PEG10 are in cortical neurons. We see that mice begin to develop neuromotor defects at around 6 weeks of age and that UBQLN2 colocalizes briefly with stress granules in mouse cortical neurons. Through these experiments, we can learn more about how UBQLN2 regulates PEG10 in primary mouse neurons, and how those neurons respond to cellular stress related to ALS. 

Date Awarded
  • 2023-04-05
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Last Modified
  • 2023-04-17
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