Mutant Mouse: Kdm6a (lysine (K)-specific demethylase 6A) (UTX Knockin Mouse)
UTX-KI. Enzyme-dead knockin (KI) mice for the histone demethylase UTX (Kdm6a) will help understand its role in tumor suppression and stem cell–mediated tissue regeneration.
Di- and tri-methylations on histone H3 lysine 27 (H3K27me2 and H3K27me3) are epigenetic marks for gene repression. UTX (ubiquitously transcribed X chromosome protein), also known as Kdm6a (lysine (K)-specific demethylase 6a), is a histone demethylase that specifically removes H3K27me2 and H3K27me3. To investigate the physiological role of UTX enzymatic activity, we have generated UTX enzyme-dead knockin mice (UTX-KI) which possess the H1146A and E1148A point mutations in exon 24 (http://www.ncbi.nlm.nih.gov/pubmed/26999603). UTX-KI mice are viable and fertile but show defects in muscle regeneration. UTX has been found to be a tumor suppressor gene mutated in a wide variety of human cancers. The UTX-KI mice provide a valuable tool to study how UTX functions as a tumor suppressor and as an epigenetic regulator of stem cell–mediated tissue regeneration.