In utero rescue of neurological dysfunction in a mouse model of Wiedemann-Steiner syndrome.

ABSTRACT: Wiedemann-Steiner syndrome (WDSTS) is a rare genetic cause of intellectual disability that is primarily caused by heterozygous loss-of-function variants in the gene encoding the histone lysine methyltransferase 2A (KMT2A). Prior studies have shown successful postnatal amelioration of disease phenotypes for Rett, Rubinstein-Taybi, and Kabuki syndromes, which are related Mendelian disorders of the epigenetic machinery. To explore whether the neurological phenotype in WDSTS is treatable in utero, we created a mouse model carrying a loss-of-function variant placed between 2 loxP sites. Kmt2a+/LSL mice demonstrated core features of WDSTS including growth retardation, craniofacial abnormalities, and hypertrichosis as well as hippocampal memory defects. The neurological phenotypes were rescued up

SUBMITTER: Reynisdottir T 

PROVIDER: S-EPMC12581663 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature