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A humanized Caenorhabditis elegans model of Hereditary Spastic Paraplegia-associated variants in kinesin light chain KLC4
A humanized Caenorhabditis elegans model of Hereditary Spastic Paraplegia-associated variants in kinesin light chain KLC4
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Length:
20 minutes
Released:
Jan 8, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.01.07.523106v1?rss=1
Authors: Gumusderelioglu, S., Resch, L., Brock, T., Undiagnosed Diseases Network,, Luxton, G. G., Tan, Q. K.-G., Hopkins, C. E., Starr, D. A.
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 homozygous, and a weak nuclear migration defect when heterozygous, possibly correlating with the clinical finding of late onset HSP when the proband was heterozygous. Thus, we were able to establish humanized C. elegans as an animal model for HSP and use it to test the significance of five variants of uncertain significance in the human gene KLC4.
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Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2023.01.07.523106v1?rss=1
Authors: Gumusderelioglu, S., Resch, L., Brock, T., Undiagnosed Diseases Network,, Luxton, G. G., Tan, Q. K.-G., Hopkins, C. E., Starr, D. A.
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 homozygous, and a weak nuclear migration defect when heterozygous, possibly correlating with the clinical finding of late onset HSP when the proband was heterozygous. Thus, we were able to establish humanized C. elegans as an animal model for HSP and use it to test the significance of five variants of uncertain significance in the human gene KLC4.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Jan 8, 2023
Format:
Podcast episode
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