MODELLING THE REPRODUCTIVE PHENOTYPES OF ADENYLOSUCCINATE LYASE DEFICIENCY IN C. ELEGANS

Open Access
Author:
Janowitz, Haley Nicole
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Dr. Wendy Hanna-Rose, Thesis Supervisor
  • Dr. Sarah Ades, Honors Advisor
Keywords:
  • adsl-1
  • C. elegans
  • purine metabolism
  • reproduction
Abstract:
Mutations in enzymes that function in purine metabolism result in human syndromes with a wide variety of symptoms. Adenylosuccinate lyase deficiency (ASLD) is characterized by the decrease in function of adenylosuccinate lyase (ADSL), a bi-functional enzyme within de novo purine biosynthesis. In humans, this syndrome is characterized by neuronal, developmental, and metabolic defects which include symptoms of seizures, encephalopathy, psychomotor retardation, and autistic features. The molecular mechanisms driving this disease are currently unknown. I report on the reproductive phenotypes associated with a knockdown of ADSL in Caenorhabditis elegans. I identify sterility in animals with significant knockdown of adsl-1 expression, as well as embryonic lethality and oogenesis defects associated with a partial knockdown of adsl-1 expression. Using supplementation, I correlate these phenotypes with a decreased flux through de novo purine biosynthesis. Although reproductive phenotypes are not directly correlated with human symptoms, these findings still have impact on the role of purines in the development of patients with ASLD.