Zebrafish models of skeletal dysplasia induced by cholesterol biosynthesis deficiency.

ABSTRACT: Human disorders of the post-squalene cholesterol biosynthesis pathway frequently result in skeletal abnormalities, yet our understanding of the mechanisms involved is limited. In a forward-genetic approach, we have found that a late-onset skeletal mutant, named koliber^nu7 , is the result of a cis-acting regulatory mutation leading to loss of methylsterol monooxygenase 1 (msmo1) expression within pre-hypertrophic chondrocytes. Generated msmo1^nu81 knockdown mutation resulted in lethality at larval stage. We demonstrated that this is a result of both cholesterol deprivation and sterol intermediate accumulation by creating a mutation eliminating activity of Lanosterol synthase (Lss). Our results indicate that double lss^nu60

SUBMITTER: Anderson RA 

PROVIDER: S-EPMC7328163 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature