Effect of damaging mutations in LXRalpha on the liver transcriptome

Damaging mutations in LXRalpha are associated with hepatotoxicity. We generated mice homozygous for a dominant-negative mutation in LXRalpha (LXRalpha-W441R) and discovered they develop severe liver injury when fed a Western diet, though knockout mice develop little to no liver injury. To examine this in further detail, we performed Bulk RNA-seq of livers from LXRalpha knockout and LXRalpha p.W441R knockin mice after 8 weeks of western diet (TD.88137). Mice carrying a dominant negative mutation in LXRalpha (p.W441R, DN) and LXRalpha knockout (KO) mice (WT-wildype, Het-heterozygous, Hom - homozygous) were fed a western diet for 8 weeks, following which they were euthanised, livers were collected at necropsy and flash frozen. Total RNAs was extracted from the mouse livers with RNeasy kit (QIAGEN).