Caenorhabditis elegans is unable to survive without the supplemental addition of cholesterol to its media and is therefore sensitive to a cholesterol-limited environment. We have shown that a mutation in a steroid metabolism gene,
let-767, results in hypersensitivity to reduced levels of cholesterol. The
let-767 gene encodes a protein that is similar to a family of mammalian steroid enzymes that are responsible for the reduction of 17-beta hydroxysteroid molecules. There are three alleles of
let-767 resulting in early larval, mid-larval, or maternal-effect lethality respectively.
let-767 is maternally contributed to the embryo and
let-767 transcripts are present during embryogenesis, however, LET-767::GFP is detectable only after hatching where it is localized specifically to the gut. We believe that
let-767 is required for the metabolism of a sterol compound in C. elegans. Four additional genes have been identified in C. elegans which have high sequence similarity to LET-767 (C06B3.4, C06B3.5, F11A5.12, and F25G6.5). All are located on chromosome V. We have evidence of expression for three of the four genes - C06B3.4, C06B3.5, and F11A5.12. F25G6.5 may be a psuedogene. We are currently investigating the role these genes play in development.