During the characterization of a null mutation of Dmel\Cpes, it was discovered that the mutant animals are sensitive to fluctuations in light intensity. Dmel\Cpes encodes an enzyme required for synthesis of ceramide phosphoethanolamine (CPE), a sphingolipid similar to sphingomyelin. When shifted from the dark to light conditions, mutants displayed classic signs of epilepsy such as seizures, paralysis, tonic-clonic-like activity, recovery seizures, refractory recovery, and complete recovery. Expression of UAS-Cpes with a pan-glial driver completely rescues the photosensitive epilepsy-like phenotypes; neural-specific or muscle-specific expression does not. Cortex glial membranes are severely compromised in Cpes mutants and fail to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex.
CPE is a structural analog of sphingomyelin, which is found in mammalian membranes. No human ortholog of Dmel\Cpes has been identified; human sphingomyelin synthases (SGMS1 and SGMS2) act in an analogous capacity. Heterologous rescue (functional complementation) is observed: expression of Hsap\SGMS1 or Hsap\SGMS2 in animals carrying mutations of Dmel\Cpes rescues the cortex glial abnormalities and photosensitive phenotypes. Other mutant phenotypes such as pupal lethality and dorsal closure defect are also rescued; male sterility is not rescued.
Other glial-sphingolipid-related diseases characterized in fly models include neuropathy, hereditary sensory and autonomic, type IA (FBhh0000473) and neuropathy, hereditary sensory and autonomic, type IB (FBhh0001015).
[updated May 2019 by FlyBase; FBrf0222196]
An epilepsy characterized by seizures triggered by visual stimuli that form patterns in space or time, such as flashing lights. [Disease Ontology, DOID:0060281; 2019.05.06]
Sphingomyelin (SM) is a vital component of mammalian membranes, providing mechanical stability and a structural framework for plasma membrane organization (Vacaru et al., 2013; pubmed:23449981).
Production of sphingomyelin involves the transfer of phosphocholine from phosphatidylcholine onto ceramide, a reaction catalyzed by sphingomyelin synthase (Vacaru et al., 2013; pubmed:23449981).
Functionally orthologous to human SGMS1 and SGMS2 (FBrf0240164).
