Introduction of a de novo Creb- binding protein gene mutation in sperm to produce a Rubinstein-Taybi Syndrome model using inbred C57BL/6 mice.

Introduction of a de novo Creb- binding protein gene mutation in sperm to produce a Rubinstein-Taybi Syndrome model using inbred C57BL/6 mice. Brain Res. 2020 Oct 03;:147140 Authors: Takagi T, Higashi Y, Asai M, Ishii S Abstract Neurodevelopmental disorders, including intellectual disability and autism spectrum disorder, are often caused by de novo autosomal dominant mutations. While mouse models are frequently used to investigate these disorders, the genetic background sometimes affects the appearance or severity of mutant phenotypes. In a previous report, we developed a system to produce de novo heterozygous mutant mice using the Cre-LoxP system without the need to maintain the heterozygous mutant line itself (Takagi et al. 2015). To further verify the applicability of the de novo mutation system in sperm, we used this system to produce a mouse model for Rubinstein-Taybi syndrome, using a Cbp heterozygous mutant, which has been reported to be difficult to maintain on a C57BL/6 background. Here, we show that de novo Cbp- loss-of-function heterozygous mutant mice with a C57BL/6 background, present with a clear craniofacial phenotype and reduced locomotor activity in the open field test, which was not observed in the loss-of-function of Cbp heterozygous mutant line mice with a mixed genetic background, but was observed in the dominant negative Cbp heterozygous mutant line with a mixed genetic background. Meanwhile, the de novo heteroz...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research