Forward genetic screening of a novel gene hmgs-1 Involved in Alzheimer Disease Pathogenesis in a transgenic Caenorhabditis elegans model.

Alzheimer disease (AD), which poses a serious challenge in aging societies, still lacks effective treatments to reverse its progression, and thus, has been a major focus of research for decades. There are several risk factors associated with the etiology of AD. To further identify potential new factors involved in AD pathogenesis, a forward genetic screening method using transgenic Caenorhabditis elegans CL4176 exposed to different temperatures was employed to screen mutant worms resistant to β-amyloid toxicity. After transcriptome sequencing, and analysis of single nucleotide polymorphism variations by RNA-Seq and DNA-Seq, it is suggested that a novel gene hmgs-1 is involved in AD pathogenesis. We verified its involvement again by the phenotype of gene knockdown mutant and the rescue effect of complementing hmgs-1. Our study provides a workable screening method for new gene mutations and a potential target of hmgs-1 in the AD pathogenesis.