A Yeast Model for Trichohepatoenteric Syndrome Suggests Strong Loss of Ski2 Function in Most Causative Mutations

Authors

Luisa J Orlando
Matthew K Yim
Thomson Hallmark
Michael Cotner
Sean J Johnson
Ambro van Hoof

Publication Date

1-1-2022

Journal

microPublication Biology

DOI

10.17912/micropub.biology.000575

PMID

35607352

PMCID

PMC9123431

PubMedCentral® Posted Date

5-20-2022

PubMedCentral® Full Text Version

Post-print

Abstract

The intestinal and immune disorder trichohepatoenteric syndrome (THES) is characterized by mutations in human Ski2 and Ski3, also known as SKIV2L and TTC37, respectively. The mechanism by which these mutations leads to the immunodeficiency, chronic diarrhea, failure to thrive and liver disease associated with THES is unknown. To what degree THES patient mutations in Ski2 affect Ski2 function and how the differences in Ski2 function could lead to varying patient outcomes has not been studied. Here, we assayed function of THES ski2 mutants in the yeast homolog. Our results show that most THES patient mutations cause severe dysfunction in Ski2. This provides the first functional analysis of these mutations and suggests that the yeast assay may be helpful in distinguishing between pathological and benign variants.

Published Open-Access

yes

Recommended Citation

Orlando, Luisa J; Yim, Matthew K; Hallmark, Thomson; et al., "A Yeast Model for Trichohepatoenteric Syndrome Suggests Strong Loss of Ski2 Function in Most Causative Mutations" (2022). Faculty, Staff and Student Publications. 3906.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/3906