Caenorhabditis elegans and its applicability to studies on restless legs syndrome

Abstract

Restless legs syndrome (RLS) is a common neurological disorder in the US. This disorder is characterized by an irresistible urge to move the legs, although the symptoms vary in a wide range. The pathobiology of RLS has been linked to iron (Fe) deficiency and dopaminergic (DAergic) dysfunction. Several genetic factors have been reported to increase the risk of RLS. Caenorhabditis elegans (C. elegans) is a well-established animal model with a fully sequenced genome, which is highly conserved with mammals. Given the detailed knowledge of its genomic architecture, ease of genetic manipulation and conserved biosynthetic and metabolic pathways, as well as its small size, ease of maintenance, speedy generation time and large brood size, C. elegans provides numerous advantages in studying RLS-associated gene-environment interactions. Here we will review current knowledge about RLS symptoms, pathology and treatments, and discuss the application of C. elegans in RLS study, including the worm homologous genes and methods that could be performed to advance the pathophysiology RLS.

Consensus guidelines on the construct validity of rodent models of restless legs syndrome

“…While these organisms cannot recapitulate the complexity of human RLS, they might provide important clues about the role of genetic risk factors in the clinical phenotype of RLS. C. elegans has several orthologs of known RLS genetic risk factors, including MEIS1 , BTBD9 and PTPRD ( unc-62 , hpo-9 and ptp-3 , respectively) ( Chen et al, 2019 ). It has eight identifiable dopaminergic neurons as well as orthologs of all the genes involved in dopamine synthesis, packaging, reuptake and metabolization ( Jayanthi et al, 1998 ; Hobert, 2013 ).…”

“…It has eight identifiable dopaminergic neurons as well as orthologs of all the genes involved in dopamine synthesis, packaging, reuptake and metabolization ( Jayanthi et al, 1998 ; Hobert, 2013 ). It also expresses several behavioral paradigms to evaluate dopaminergic function ( Chen et al, 2019 ). The dop-1 and dop-3 genes encode for C. elegans dopamine receptors.…”

Do genes matter in sleep?-A comprehensive update

“…Diagnostic criteria of RLS is quite simple [47]. Mode of inheritance can be AD, AR and few cases are not clear.…”