Drosophila melanogaster Potential as a Model System for Human Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency
Faculty Mentor
Luis Matos
Document Type
Poster
Start Date
10-5-2023 9:00 AM
End Date
10-5-2023 10:45 AM
Location
PUB NCR
Department
Biology
Abstract
Succinic semialdehyde dehydrogenase (SSADH) functions in gamma-aminobutyric acid (GABA) catabolism by converting succinic semialdehyde (SSA) into succinic acid. Proper GABA synthesis and breakdown is essential for GABA to perform its primary role as an inhibitory neurotransmitter in the central nervous system (CNS). Mutations in the SSADH gene produce SSADH deficiency, a rare genetic disorder in humans. This deficiency yields a buildup of GABA and SSA, allowing 4-hydroxybutyrate dehydrogenase (4-HBAD) to convert SSA into gamma-hydroxybutyric acid (GHB) and 4-hydroxybutyric acid (4-HBA). The buildup of GHB in the CNS results in many symptoms, including developmental, musculoskeletal, and neurological aberrations. To find a treatment for the deficiency, researchers developed and currently use a mouse model. In the model, mice with the deficiency have an increased concentration of GHB, SSA, and 4-HBA. High concentrations of GHB in the mice cause absence-like seizures. When the mice reach the post-natal (PN) age of 14-18 days, the seizures progress to a lethal status of epilepsy resulting in the death of the mice at PN age of 20-26 days. As the mouse model is expensive to maintain and the mice die, here we test the hypothesis that Drosophila melanogaster with gene knockouts for the SSADH homolog can serve as a model for SSADH deficiency. Our first objective is to identify a trait/behavior that associates with the SSADH deficiency in D. melanogaster. The second objective is to test whether the trait/behavior can be manipulated. Various behavioral and developmental assays were tested with mutant and wild-type flies. Our results indicate a significant difference in recuperation time (after CO2 anesthesia) exists between the wild-type and mutant and SSADH- flies. Exacerbation of this behavior is currently being tested. Successful manipulation of the recuperation phenotype would suggest that D. melanogaster could serve as a model for testing potential therapeutic compounds.
Recommended Citation
Kaddoura, Mohammad and Shahrabadi, Shayan, "Drosophila melanogaster Potential as a Model System for Human Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency" (2023). 2023 Symposium. 27.
https://dc.ewu.edu/srcw_2023/res_2023/p1_2023/27
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Drosophila melanogaster Potential as a Model System for Human Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency
PUB NCR
Succinic semialdehyde dehydrogenase (SSADH) functions in gamma-aminobutyric acid (GABA) catabolism by converting succinic semialdehyde (SSA) into succinic acid. Proper GABA synthesis and breakdown is essential for GABA to perform its primary role as an inhibitory neurotransmitter in the central nervous system (CNS). Mutations in the SSADH gene produce SSADH deficiency, a rare genetic disorder in humans. This deficiency yields a buildup of GABA and SSA, allowing 4-hydroxybutyrate dehydrogenase (4-HBAD) to convert SSA into gamma-hydroxybutyric acid (GHB) and 4-hydroxybutyric acid (4-HBA). The buildup of GHB in the CNS results in many symptoms, including developmental, musculoskeletal, and neurological aberrations. To find a treatment for the deficiency, researchers developed and currently use a mouse model. In the model, mice with the deficiency have an increased concentration of GHB, SSA, and 4-HBA. High concentrations of GHB in the mice cause absence-like seizures. When the mice reach the post-natal (PN) age of 14-18 days, the seizures progress to a lethal status of epilepsy resulting in the death of the mice at PN age of 20-26 days. As the mouse model is expensive to maintain and the mice die, here we test the hypothesis that Drosophila melanogaster with gene knockouts for the SSADH homolog can serve as a model for SSADH deficiency. Our first objective is to identify a trait/behavior that associates with the SSADH deficiency in D. melanogaster. The second objective is to test whether the trait/behavior can be manipulated. Various behavioral and developmental assays were tested with mutant and wild-type flies. Our results indicate a significant difference in recuperation time (after CO2 anesthesia) exists between the wild-type and mutant and SSADH- flies. Exacerbation of this behavior is currently being tested. Successful manipulation of the recuperation phenotype would suggest that D. melanogaster could serve as a model for testing potential therapeutic compounds.
