Generating Saccharomyces cerevisiae models of Lenz-Majewski Syndrome for cellular and genetic studies

JULS Volume 10, Issue 1

Wan Ting Huang1

1 Faculty of Arts and Science, University of Toronto

Corresponding Author: Wan Ting Huang (


As the only known human disease caused by disrupted phosphatidylserine (PS) metabolism, Lenz-Majewski syndrome can offer insight into the physiologically important, yet not well understood PS pathway. Saccharomyces cerevisiae (budding yeast) was used to produce working models of the disease for genetic and cellular studies, which to the author’s knowledge are the only models available for Lenz-Majewski Syndrome. PS expression levels in yeast were manipulated using a combination of wild-type, PS decarboxylase 1 knockout (psd1Δ ), or psd1 /psd2Δ  cells and overexpression of plasmid borne CHO1 that encodes PS synthase. Experiments investigated cell growth, cellular PS distribution, and global PS levels to confirm and further define phenotypes. Results show extensively impaired cell growth in all psd1 /psd2Δ  cells, especially for psd1Δ  cells that constitutively expressed CHO1. In parallel experiments using galactose inducible plasmids, wild-type and psd1Δ  cells that overexpressed CHO1 on galactose plates regained non-glucose associated phospholipid depletion and grew better compared to counterparts transformed with vector. Analysis of PS distribution revealed increasingly aberrant PS accumulation in early endosomes and vesicles for wild-type cells that overexpressed CHO1, psd1Δ  cells with vector, and psd1Δ  cells that overexpressed CHO1. Similarly, cells experienced loss of polarity and were larger and rounder. Psd1Δ  cells that overexpressed CHO1 were on average 99.7% greater in area compared to wild-type cells. Attempts to investigate global PS levels were unsuccessful. The study reveals that high PS levels result in impaired cell growth and PS accumulation in intracellular structures.