A humanized Caenorhabditis elegans model of Hereditary Spastic Paraplegia-associated variants in kinesin light chain KLC4.

ABSTRACT: Hereditary spastic paraplegia (HSP) is a group of degenerative neurological disorders. We identified a variant in human kinesin light chain KLC4 that is suspected to be associated with autosomal dominant HSP. How this and other variants relate to pathologies is unknown. We created a humanized C. elegans model where klc- 2 was replaced with human KLC4 and assessed the extent to which hKLC4 retained function in the worm. We observed a slight decrease in motility but no nuclear migration defects in the humanized worms, suggesting that hKLC4 retains much of the function of klc-2 . Five hKLC4 variants were introduced into the humanized model. The clinical variant led to early lethality with significant defects in nuclear migration when hom

SUBMITTER: Gumusderelioglu S 

PROVIDER: S-EPMC9928042 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature